RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers
Identifieur interne : 000492 ( Main/Exploration ); précédent : 000491; suivant : 000493RNF208, 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.
Url:
DOI: 10.1038/s41467-019-13852-5
PubMed: 31862882
PubMed Central: 6925134
Affiliations:
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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="3"><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><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></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><affiliations><list><country><li>Corée du Sud</li><li>Japon</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><noCountry><name sortKey="Kim, Seong Jin" sort="Kim, Seong Jin" uniqKey="Kim S" first="Seong-Jin" last="Kim">Seong-Jin Kim</name><name sortKey="Lee, Jihee" sort="Lee, Jihee" uniqKey="Lee J" first="Jihee" last="Lee">Jihee Lee</name><name sortKey="Lee, So Young" sort="Lee, So Young" uniqKey="Lee S" first="So-Young" last="Lee">So-Young Lee</name><name sortKey="Mizuno, Seiya" sort="Mizuno, Seiya" uniqKey="Mizuno S" first="Seiya" last="Mizuno">Seiya Mizuno</name><name sortKey="Ooshima, Akira" sort="Ooshima, Akira" uniqKey="Ooshima A" first="Akira" last="Ooshima">Akira Ooshima</name><name sortKey="Pang, Kyoungwha" sort="Pang, Kyoungwha" uniqKey="Pang K" first="Kyoungwha" last="Pang">Kyoungwha Pang</name><name sortKey="Park, Jinah" sort="Park, Jinah" uniqKey="Park J" first="Jinah" last="Park">Jinah Park</name><name sortKey="Park, Kyung Soon" sort="Park, Kyung Soon" uniqKey="Park K" first="Kyung-Soon" last="Park">Kyung-Soon Park</name><name sortKey="Park, Yuna" sort="Park, Yuna" uniqKey="Park Y" first="Yuna" last="Park">Yuna Park</name><name sortKey="Yang, Kyung Min" sort="Yang, Kyung Min" uniqKey="Yang K" first="Kyung-Min" last="Yang">Kyung-Min Yang</name></noCountry><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Ahn, Sung Gwe" sort="Ahn, Sung Gwe" uniqKey="Ahn S" first="Sung Gwe" last="Ahn">Sung Gwe Ahn</name></region><name sortKey="Jeong, Joon" sort="Jeong, Joon" uniqKey="Jeong J" first="Joon" last="Jeong">Joon Jeong</name></country><country name="Japon"><noRegion><name sortKey="Yamashita, Satoshi" sort="Yamashita, Satoshi" uniqKey="Yamashita S" first="Satoshi" last="Yamashita">Satoshi Yamashita</name></noRegion><name sortKey="Ushijima, Toshikazu" sort="Ushijima, Toshikazu" uniqKey="Ushijima T" first="Toshikazu" last="Ushijima">Toshikazu Ushijima</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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