Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy
Identifieur interne : 000676 ( Main/Exploration ); précédent : 000675; suivant : 000677Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy
Auteurs : Mi-Gi Lee [Corée du Sud] ; Min-Ah Choi [Corée du Sud] ; Sehyun Chae [Corée du Sud] ; Mi-Ae Kang [Corée du Sud] ; Hantae Jo [Corée du Sud] ; Jin-Myoung Baek [Corée du Sud] ; Kyu-Ree In [Corée du Sud] ; Hyein Park [Corée du Sud] ; Hyojin Heo [Corée du Sud] ; Dongmin Jang [Corée du Sud] ; Sofia Brito [Corée du Sud] ; Sung Tae Kim [Corée du Sud] ; Dae-Ok Kim [Corée du Sud] ; Jong-Soo Lee [Corée du Sud] ; Jae-Ryong Kim [Corée du Sud] ; Bum-Ho Bin [Corée du Sud]Source :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13−/− cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13−/− cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2’-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13−/− cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.
Url:
DOI: 10.1038/s41598-019-51438-9
PubMed: 31636298
PubMed Central: 6803768
Affiliations:
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0001 2171 7818</institution-id><institution-id institution-id-type="GRID">grid.289247.2</institution-id><institution>Department of Food Science and Technology, College of Life Sciences,</institution><institution>Kyung Hee University,</institution></institution-wrap>Yongin, 446-701 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Yongin</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Min Ah" sort="Choi, Min Ah" uniqKey="Choi M" first="Min-Ah" last="Choi">Min-Ah Choi</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0674 4447</institution-id><institution-id institution-id-type="GRID">grid.413028.c</institution-id><institution>Department of Biochemistry and Molecular Biology,</institution><institution>Yeungnam University College of Medicine,</institution></institution-wrap>Daegu, 42415 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Daegu</wicri:regionArea></affiliation></author><author><name sortKey="Chae, Sehyun" sort="Chae, Sehyun" uniqKey="Chae S" first="Sehyun" last="Chae">Sehyun Chae</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Korea Brain Bank, Korean Brain Research Institute, Daegu, 41062 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korea Brain Bank, Korean Brain Research Institute, Daegu</wicri:regionArea><wicri:noRegion>Daegu</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Mi Ae" sort="Kang, Mi Ae" uniqKey="Kang M" first="Mi-Ae" last="Kang">Mi-Ae Kang</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0532 3933</institution-id><institution-id institution-id-type="GRID">grid.251916.8</institution-id><institution>Department of Bological Sciences,</institution><institution>Ajou University,</institution></institution-wrap>Suwon, 443-380 Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Jo, Hantae" sort="Jo, Hantae" uniqKey="Jo H" first="Hantae" last="Jo">Hantae Jo</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0532 3933</institution-id><institution-id institution-id-type="GRID">grid.251916.8</institution-id><institution>Department of Bological Sciences,</institution><institution>Ajou University,</institution></institution-wrap>Suwon, 443-380 Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Baek, Jin Myoung" sort="Baek, Jin Myoung" uniqKey="Baek J" first="Jin-Myoung" last="Baek">Jin-Myoung Baek</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0532 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wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0674 4447</institution-id><institution-id institution-id-type="GRID">grid.413028.c</institution-id><institution>Department of Biochemistry and Molecular Biology,</institution><institution>Yeungnam University College of Medicine,</institution></institution-wrap>Daegu, 42415 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Daegu</wicri:regionArea></affiliation></author><author><name sortKey="Bin, Bum Ho" sort="Bin, Bum Ho" uniqKey="Bin B" first="Bum-Ho" last="Bin">Bum-Ho Bin</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0532 3933</institution-id><institution-id institution-id-type="GRID">grid.251916.8</institution-id><institution>Department of Bological Sciences,</institution><institution>Ajou University,</institution></institution-wrap>Suwon, 443-380 Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</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">Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13<sup>−/−</sup> cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13<sup>−/−</sup> cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2’-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13<sup>−/−</sup> cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Schneider, G" uniqKey="Schneider G">G Schneider</name></author><author><name sortKey="Schmidt Supprian, M" uniqKey="Schmidt Supprian M">M Schmidt-Supprian</name></author><author><name sortKey="Rad, R" uniqKey="Rad R">R Rad</name></author><author><name sortKey="Saur, D" uniqKey="Saur D">D Saur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Folpe, Al" uniqKey="Folpe A">AL Folpe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mathew, R" uniqKey="Mathew R">R Mathew</name></author><author><name sortKey="Karantza Wadsworth, V" uniqKey="Karantza Wadsworth V">V Karantza-Wadsworth</name></author><author><name sortKey="White, E" uniqKey="White E">E White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, E" uniqKey="White E">E White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glick, D" uniqKey="Glick D">D Glick</name></author><author><name sortKey="Barth, S" uniqKey="Barth S">S Barth</name></author><author><name sortKey="Macleod, Kf" uniqKey="Macleod K">KF Macleod</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T Yoshimori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rubinsztein, Dc" uniqKey="Rubinsztein D">DC Rubinsztein</name></author><author><name sortKey="Marino, G" uniqKey="Marino G">G Marino</name></author><author><name sortKey="Kroemer, G" uniqKey="Kroemer G">G Kroemer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanida, I" uniqKey="Tanida I">I Tanida</name></author><author><name sortKey="Ueno, T" uniqKey="Ueno T">T Ueno</name></author><author><name sortKey="Kominami, E" uniqKey="Kominami E">E Kominami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hara, T" uniqKey="Hara T">T Hara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukada, T" uniqKey="Fukada T">T Fukada</name></author><author><name sortKey="Kambe, T" uniqKey="Kambe T">T Kambe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author><author><name sortKey="Seo, J" uniqKey="Seo J">J Seo</name></author><author><name sortKey="Kim, St" uniqKey="Kim S">ST Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liuzzi, Jp" uniqKey="Liuzzi J">JP Liuzzi</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L Guo</name></author><author><name sortKey="Yoo, C" uniqKey="Yoo C">C Yoo</name></author><author><name sortKey="Stewart, Ts" uniqKey="Stewart T">TS Stewart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hwang, Jj" uniqKey="Hwang J">JJ Hwang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Summersgill, H" uniqKey="Summersgill H">H Summersgill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Z" uniqKey="Liu Z">Z Liu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukada, T" uniqKey="Fukada T">T Fukada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tycko, B" uniqKey="Tycko B">B Tycko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamasaki, S" uniqKey="Yamasaki S">S Yamasaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakatogawa, H" uniqKey="Nakatogawa H">H Nakatogawa</name></author><author><name sortKey="Suzuki, K" uniqKey="Suzuki K">K Suzuki</name></author><author><name sortKey="Kamada, Y" uniqKey="Kamada Y">Y Kamada</name></author><author><name sortKey="Ohsumi, Y" uniqKey="Ohsumi Y">Y Ohsumi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name></author><author><name sortKey="Emr, Sd" uniqKey="Emr S">SD Emr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Batlevi, Y" uniqKey="Batlevi Y">Y Batlevi</name></author><author><name sortKey="La Spada, Ar" uniqKey="La Spada A">AR La Spada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barnett, A" uniqKey="Barnett A">A Barnett</name></author><author><name sortKey="Brewer, Gj" uniqKey="Brewer G">GJ Brewer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, H" uniqKey="He H">H He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Othman, Eq" uniqKey="Othman E">EQ Othman</name></author><author><name sortKey="Kaur, G" uniqKey="Kaur G">G Kaur</name></author><author><name sortKey="Mutee, Af" uniqKey="Mutee A">AF Mutee</name></author><author><name sortKey="Muhammad, Ts" uniqKey="Muhammad T">TS Muhammad</name></author><author><name sortKey="Tan, Ml" uniqKey="Tan M">ML Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujishiro, H" uniqKey="Fujishiro H">H Fujishiro</name></author><author><name sortKey="Okugaki, S" uniqKey="Okugaki S">S Okugaki</name></author><author><name sortKey="Yasumitsu, S" uniqKey="Yasumitsu S">S Yasumitsu</name></author><author><name sortKey="Enomoto, S" uniqKey="Enomoto S">S Enomoto</name></author><author><name sortKey="Himeno, S" uniqKey="Himeno S">S Himeno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, G" uniqKey="Jiang G">G Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bestor, Th" uniqKey="Bestor T">TH Bestor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poirier, La" uniqKey="Poirier L">LA Poirier</name></author><author><name sortKey="Vlasova, Ti" uniqKey="Vlasova T">TI 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uniqKey="Miyai T">T Miyai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Velazquez Delgado, Em" uniqKey="Velazquez Delgado E">EM Velazquez-Delgado</name></author><author><name sortKey="Hardy, Ja" uniqKey="Hardy J">JA Hardy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huber, Kl" uniqKey="Huber K">KL Huber</name></author><author><name sortKey="Hardy, Ja" uniqKey="Hardy J">JA Hardy</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, Bh" uniqKey="Bin B">BH Bin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Lee, Mi Gi" sort="Lee, Mi Gi" uniqKey="Lee M" first="Mi-Gi" last="Lee">Mi-Gi Lee</name></noRegion><name sortKey="Baek, Jin Myoung" sort="Baek, Jin Myoung" uniqKey="Baek J" first="Jin-Myoung" last="Baek">Jin-Myoung Baek</name><name sortKey="Bin, Bum Ho" sort="Bin, Bum Ho" uniqKey="Bin B" first="Bum-Ho" last="Bin">Bum-Ho Bin</name><name sortKey="Brito, Sofia" sort="Brito, Sofia" uniqKey="Brito S" first="Sofia" last="Brito">Sofia Brito</name><name sortKey="Chae, Sehyun" sort="Chae, Sehyun" uniqKey="Chae S" first="Sehyun" last="Chae">Sehyun Chae</name><name sortKey="Choi, Min Ah" sort="Choi, Min Ah" uniqKey="Choi M" first="Min-Ah" last="Choi">Min-Ah Choi</name><name sortKey="Heo, Hyojin" sort="Heo, Hyojin" uniqKey="Heo H" first="Hyojin" last="Heo">Hyojin Heo</name><name sortKey="In, Kyu Ree" sort="In, Kyu Ree" uniqKey="In K" first="Kyu-Ree" last="In">Kyu-Ree In</name><name sortKey="Jang, Dongmin" sort="Jang, Dongmin" uniqKey="Jang D" first="Dongmin" last="Jang">Dongmin Jang</name><name sortKey="Jo, Hantae" sort="Jo, Hantae" uniqKey="Jo H" first="Hantae" last="Jo">Hantae Jo</name><name sortKey="Kang, Mi Ae" sort="Kang, Mi Ae" uniqKey="Kang M" first="Mi-Ae" last="Kang">Mi-Ae Kang</name><name sortKey="Kim, Dae Ok" sort="Kim, Dae Ok" uniqKey="Kim D" first="Dae-Ok" last="Kim">Dae-Ok Kim</name><name sortKey="Kim, Dae Ok" sort="Kim, Dae Ok" uniqKey="Kim D" first="Dae-Ok" last="Kim">Dae-Ok Kim</name><name sortKey="Kim, Jae Ryong" sort="Kim, Jae Ryong" uniqKey="Kim J" first="Jae-Ryong" last="Kim">Jae-Ryong Kim</name><name sortKey="Kim, Sung Tae" sort="Kim, Sung Tae" uniqKey="Kim S" first="Sung Tae" last="Kim">Sung Tae Kim</name><name sortKey="Lee, Jong Soo" sort="Lee, Jong Soo" uniqKey="Lee J" first="Jong-Soo" last="Lee">Jong-Soo Lee</name><name sortKey="Park, Hyein" sort="Park, Hyein" uniqKey="Park H" first="Hyein" last="Park">Hyein Park</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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