Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy
Identifieur interne : 000B24 ( Ncbi/Merge ); précédent : 000B23; suivant : 000B25Loss 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
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PMC:6803768Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy</title>
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<author><name sortKey="Lee, Jong Soo" sort="Lee, Jong Soo" uniqKey="Lee J" first="Jong-Soo" last="Lee">Jong-Soo Lee</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="Kim, Jae Ryong" sort="Kim, Jae Ryong" uniqKey="Kim J" first="Jae-Ryong" last="Kim">Jae-Ryong Kim</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="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>
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<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>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group><journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</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">31636298</article-id>
<article-id pub-id-type="pmc">6803768</article-id>
<article-id pub-id-type="publisher-id">51438</article-id>
<article-id pub-id-type="doi">10.1038/s41598-019-51438-9</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Loss of the dermis zinc transporter ZIP13 promotes the mildness of fibrosarcoma by inhibiting autophagy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lee</surname>
<given-names>Mi-Gi</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Choi</surname>
<given-names>Min-Ah</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Chae</surname>
<given-names>Sehyun</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kang</surname>
<given-names>Mi-Ae</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jo</surname>
<given-names>Hantae</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baek</surname>
<given-names>Jin-myoung</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>In</surname>
<given-names>Kyu-Ree</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Park</surname>
<given-names>Hyein</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Heo</surname>
<given-names>Hyojin</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jang</surname>
<given-names>Dongmin</given-names>
</name>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brito</surname>
<given-names>Sofia</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Sung Tae</given-names>
</name>
<xref ref-type="aff" rid="Aff6">6</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-9262-1354</contrib-id>
<name><surname>Kim</surname>
<given-names>Dae-Ok</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Jong-Soo</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Kim</surname>
<given-names>Jae-Ryong</given-names>
</name>
<address><email>kimjr000@gmail.com</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-3312-702X</contrib-id>
<name><surname>Bin</surname>
<given-names>Bum-Ho</given-names>
</name>
<address><email>bhb@ajou.ac.kr</email>
</address>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 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</aff>
<aff id="Aff2"><label>2</label>
<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</aff>
<aff id="Aff3"><label>3</label>
Korea Brain Bank, Korean Brain Research Institute, Daegu, 41062 Republic of Korea</aff>
<aff id="Aff4"><label>4</label>
<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</aff>
<aff id="Aff5"><label>5</label>
<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 Biomedical Sciences, Major in Molecular Medicine,</institution>
<institution>Ajou University Graduate School,</institution>
</institution-wrap>
Suwon, South Korea</aff>
<aff id="Aff6"><label>6</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0470 5112</institution-id>
<institution-id institution-id-type="GRID">grid.411612.1</institution-id>
<institution>Department of Pharmaceutical Engineering,</institution>
<institution>Inje University,</institution>
</institution-wrap>
Gimhae-si, 50834 Korea</aff>
<aff id="Aff7"><label>7</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2171 7818</institution-id>
<institution-id institution-id-type="GRID">grid.289247.2</institution-id>
<institution>Graduate School of Biotechnology,</institution>
<institution>Kyung Hee University,</institution>
</institution-wrap>
Yongin, 446-701 Republic of Korea</aff>
</contrib-group>
<pub-date pub-type="epub"><day>21</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>21</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>9</volume>
<elocation-id>15042</elocation-id>
<history><date date-type="received"><day>19</day>
<month>2</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>30</day>
<month>9</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>
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.</license-p>
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<abstract id="Abs1"><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>
</abstract>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Cancer metabolism</kwd>
<kwd>Sarcoma</kwd>
</kwd-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>
<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>
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