RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers
Identifieur interne : 000150 ( Pmc/Curation ); précédent : 000149; suivant : 000151RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers
Auteurs : Kyoungwha Pang ; Jinah Park ; Sung Gwe Ahn [Corée du Sud] ; Jihee Lee ; Yuna Park ; Akira Ooshima ; Seiya Mizuno ; Satoshi Yamashita [Japon] ; Kyung-Soon Park ; So-Young Lee ; Joon Jeong [Corée du Sud] ; Toshikazu Ushijima [Japon] ; Kyung-Min Yang ; Seong-Jin KimSource :
- Nature Communications [ 2041-1723 ] ; 2019.
Abstract
The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.
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DOI: 10.1038/s41467-019-13852-5
PubMed: 31862882
PubMed Central: 6925134
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Kyoungwha Pang<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department 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institution-id-type="GRID">grid.20515.33</institution-id><institution>Laboratory Animal Resource Center,</institution><institution>University of Tsukuba,</institution></institution-wrap>Tsukuba, Ibaraki 305-8575 Japan</nlm:aff><wicri:noCountry code="subfield">Ibaraki 305-8575 Japan</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Internal Medicine,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8">TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8">TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8">TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation>Le document en format XML
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Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Ooshima, Akira" sort="Ooshima, Akira" uniqKey="Ooshima A" first="Akira" last="Ooshima">Akira Ooshima</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Mizuno, Seiya" sort="Mizuno, Seiya" uniqKey="Mizuno S" first="Seiya" last="Mizuno">Seiya Mizuno</name><affiliation><nlm:aff 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xml:lang="fr">Japon</country><wicri:regionArea>Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Park, Kyung Soon" sort="Park, Kyung Soon" uniqKey="Park K" first="Kyung-Soon" last="Park">Kyung-Soon Park</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Lee, So Young" sort="Lee, So Young" uniqKey="Lee S" first="So-Young" last="Lee">So-Young Lee</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Internal Medicine,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Jeong, Joon" sort="Jeong, Joon" uniqKey="Jeong J" first="Joon" last="Jeong">Joon Jeong</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5454</institution-id><institution-id institution-id-type="GRID">grid.15444.30</institution-id><institution>Department of Surgery, Gangnam Severance Hospital,</institution><institution>Yonsei University Medical College,</institution></institution-wrap>712 Eonjuro, Gangnam-Gu, Seoul, 135-720 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>712 Eonjuro, Gangnam-Gu, Seoul</wicri:regionArea></affiliation></author><author><name sortKey="Ushijima, Toshikazu" sort="Ushijima, Toshikazu" uniqKey="Ushijima T" first="Toshikazu" last="Ushijima">Toshikazu Ushijima</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Epigenomics,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Kyung Min" sort="Yang, Kyung Min" uniqKey="Yang K" first="Kyung-Min" last="Yang">Kyung-Min Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Seong Jin" sort="Kim, Seong Jin" uniqKey="Kim S" first="Seong-Jin" last="Kim">Seong-Jin Kim</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8">TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31862882</idno><idno type="pmc">6925134</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925134</idno><idno type="RBID">PMC:6925134</idno><idno type="doi">10.1038/s41467-019-13852-5</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000150</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000150</idno><idno type="wicri:Area/Pmc/Curation">000150</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000150</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers</title><author><name sortKey="Pang, Kyoungwha" sort="Pang, Kyoungwha" uniqKey="Pang K" first="Kyoungwha" last="Pang">Kyoungwha Pang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Park, Jinah" sort="Park, Jinah" uniqKey="Park J" first="Jinah" last="Park">Jinah Park</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Ahn, Sung Gwe" sort="Ahn, Sung Gwe" uniqKey="Ahn S" first="Sung Gwe" last="Ahn">Sung Gwe Ahn</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5454</institution-id><institution-id institution-id-type="GRID">grid.15444.30</institution-id><institution>Department of Surgery, Gangnam Severance Hospital,</institution><institution>Yonsei University Medical College,</institution></institution-wrap>712 Eonjuro, Gangnam-Gu, Seoul, 135-720 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>712 Eonjuro, Gangnam-Gu, Seoul</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Jihee" sort="Lee, Jihee" uniqKey="Lee J" first="Jihee" last="Lee">Jihee Lee</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Park, Yuna" sort="Park, Yuna" uniqKey="Park Y" first="Yuna" last="Park">Yuna Park</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Ooshima, Akira" sort="Ooshima, Akira" uniqKey="Ooshima A" first="Akira" last="Ooshima">Akira Ooshima</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Mizuno, Seiya" sort="Mizuno, Seiya" uniqKey="Mizuno S" first="Seiya" last="Mizuno">Seiya Mizuno</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2369 4728</institution-id><institution-id institution-id-type="GRID">grid.20515.33</institution-id><institution>Laboratory Animal Resource Center,</institution><institution>University of Tsukuba,</institution></institution-wrap>Tsukuba, Ibaraki 305-8575 Japan</nlm:aff><wicri:noCountry code="subfield">Ibaraki 305-8575 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Yamashita, Satoshi" sort="Yamashita, Satoshi" uniqKey="Yamashita S" first="Satoshi" last="Yamashita">Satoshi Yamashita</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Epigenomics,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Park, Kyung Soon" sort="Park, Kyung Soon" uniqKey="Park K" first="Kyung-Soon" last="Park">Kyung-Soon Park</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Lee, So Young" sort="Lee, So Young" uniqKey="Lee S" first="So-Young" last="Lee">So-Young Lee</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Internal Medicine,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 463-400 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Jeong, Joon" sort="Jeong, Joon" uniqKey="Jeong J" first="Joon" last="Jeong">Joon Jeong</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5454</institution-id><institution-id institution-id-type="GRID">grid.15444.30</institution-id><institution>Department of Surgery, Gangnam Severance Hospital,</institution><institution>Yonsei University Medical College,</institution></institution-wrap>712 Eonjuro, Gangnam-Gu, Seoul, 135-720 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>712 Eonjuro, Gangnam-Gu, Seoul</wicri:regionArea></affiliation></author><author><name sortKey="Ushijima, Toshikazu" sort="Ushijima, Toshikazu" uniqKey="Ushijima T" first="Toshikazu" last="Ushijima">Toshikazu Ushijima</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Epigenomics,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>Tokyo, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Kyung Min" sort="Yang, Kyung Min" uniqKey="Yang K" first="Kyung-Min" last="Yang">Kyung-Min Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Seong Jin" sort="Kim, Seong Jin" uniqKey="Kim S" first="Seong-Jin" last="Kim">Seong-Jin Kim</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff8">TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggi-do 16229 Republic of Korea</wicri:noCountry></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Desantis, C" uniqKey="Desantis C">C DeSantis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sotiriou, C" uniqKey="Sotiriou C">C Sotiriou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lower, Ee" uniqKey="Lower E">EE Lower</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mandlekar, S" uniqKey="Mandlekar S">S Mandlekar</name></author><author><name sortKey="Kong, An" uniqKey="Kong A">AN Kong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masuda, H" uniqKey="Masuda H">H Masuda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Jq" uniqKey="Chen J">JQ Chen</name></author><author><name sortKey="Russo, J" uniqKey="Russo J">J Russo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giacinti, L" uniqKey="Giacinti L">L Giacinti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keen, Jc" uniqKey="Keen J">JC Keen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satelli, A" uniqKey="Satelli A">A Satelli</name></author><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eriksson, Je" uniqKey="Eriksson J">JE Eriksson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cogli, L" uniqKey="Cogli L">L Cogli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snider, Nt" uniqKey="Snider N">NT Snider</name></author><author><name sortKey="Omary, Mb" uniqKey="Omary M">MB Omary</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snider, Nt" uniqKey="Snider N">NT Snider</name></author><author><name sortKey="Omary, Mb" uniqKey="Omary M">MB Omary</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, L" uniqKey="Zhao L">L Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gyorffy, B" uniqKey="Gyorffy B">B Gyorffy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Inagaki, M" uniqKey="Inagaki M">M Inagaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, Qs" uniqKey="Zhu Q">QS Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferguson, At" uniqKey="Ferguson A">AT Ferguson</name></author><author><name sortKey="Lapidus, Rg" uniqKey="Lapidus R">RG Lapidus</name></author><author><name sortKey="Davidson, Ne" uniqKey="Davidson N">NE Davidson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reese, Jm" uniqKey="Reese J">JM Reese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reese, Jm" uniqKey="Reese J">JM Reese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, C" uniqKey="Thomas C">C Thomas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ivaska, J" uniqKey="Ivaska J">J Ivaska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dickson, Rb" uniqKey="Dickson R">RB Dickson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ran, Fa" uniqKey="Ran F">FA Ran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klockenbusch, C" uniqKey="Klockenbusch C">C Klockenbusch</name></author><author><name sortKey="Kast, J" uniqKey="Kast J">J Kast</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riaz, M" uniqKey="Riaz M">M Riaz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iorio, F" uniqKey="Iorio F">F Iorio</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31862882</article-id><article-id pub-id-type="pmc">6925134</article-id><article-id pub-id-type="publisher-id">13852</article-id><article-id pub-id-type="doi">10.1038/s41467-019-13852-5</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-4172-5350</contrib-id><name><surname>Pang</surname><given-names>Kyoungwha</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Jinah</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ahn</surname><given-names>Sung Gwe</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Jihee</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Yuna</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ooshima</surname><given-names>Akira</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mizuno</surname><given-names>Seiya</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Yamashita</surname><given-names>Satoshi</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Kyung-Soon</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>So-Young</given-names></name><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Jeong</surname><given-names>Joon</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-3405-7817</contrib-id><name><surname>Ushijima</surname><given-names>Toshikazu</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Yang</surname><given-names>Kyung-Min</given-names></name><address><email>yangkm@snu.ac.kr</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Kim</surname><given-names>Seong-Jin</given-names></name><address><email>jasonsjkim@snu.ac.kr</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff7">7</xref><xref ref-type="aff" rid="Aff8">8</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Precision Medicine Research Center, Advanced Institute of Convergence Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Biomedical Science, College of Life Science,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5454</institution-id><institution-id institution-id-type="GRID">grid.15444.30</institution-id><institution>Department of Surgery, Gangnam Severance Hospital,</institution><institution>Yonsei University Medical College,</institution></institution-wrap>712 Eonjuro, Gangnam-Gu, Seoul, 135-720 Republic of Korea</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2369 4728</institution-id><institution-id institution-id-type="GRID">grid.20515.33</institution-id><institution>Laboratory Animal Resource Center,</institution><institution>University of Tsukuba,</institution></institution-wrap>Tsukuba, Ibaraki 305-8575 Japan</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2168 5385</institution-id><institution-id institution-id-type="GRID">grid.272242.3</institution-id><institution>Division of Epigenomics,</institution><institution>National Cancer Center Research Institute,</institution></institution-wrap>Tokyo, Japan</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0647 3511</institution-id><institution-id institution-id-type="GRID">grid.410886.3</institution-id><institution>Department of Internal Medicine,</institution><institution>CHA University,</institution></institution-wrap>Seongnam City, Gyeonggi-do 463-400 Republic of Korea</aff><aff id="Aff7"><label>7</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5905</institution-id><institution-id institution-id-type="GRID">grid.31501.36</institution-id><institution>Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology,</institution><institution>Seoul National University,</institution></institution-wrap>Suwon, Gyeonggi-do 16229 Republic of Korea</aff><aff id="Aff8"><label>8</label>TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229 Republic of Korea</aff></contrib-group><pub-date pub-type="epub"><day>20</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>5805</elocation-id><history><date date-type="received"><day>21</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>3</day><month>12</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies. Here, the authors show that RNF208, an estrogen-induced ubiquitin ligase, promotes the degradation of Vimentin, thereby suppressing lung metastasis of TNBC, and may serve as a biomarker for the disease.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Breast cancer</kwd><kwd>Cell invasion</kwd></kwd-group><funding-group><award-group><funding-source><institution>K.-M. Yang is the recipient of a National Research Foundation grant of Korea (NRF-2017R1D1A1B03035390) funded by the Ministry of Education.</institution></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution>This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037).</institution></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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