The Role of ZNF143 in Breast Cancer Cell Survival Through the NAD(P)H Quinone Dehydrogenase 1–p53–Beclin1 Axis Under Metabolic Stress
Identifieur interne : 000356 ( Main/Exploration ); précédent : 000355; suivant : 000357The Role of ZNF143 in Breast Cancer Cell Survival Through the NAD(P)H Quinone Dehydrogenase 1–p53–Beclin1 Axis Under Metabolic Stress
Auteurs : A Rome Paek ; Ji Young Mun ; Mun Jeong Jo ; Hyosun Choi ; Yun Jeong Lee ; Heesun Cheong [Corée du Sud] ; Jae Kyung Myung ; Dong Wan Hong ; Jongkeun Park ; Kyung-Hee Kim ; Hye Jin YouSource :
- Cells [ 2073-4409 ] ; 2019.
Abstract
Autophagy is a cellular process that disrupts and uses unnecessary or malfunctioning components for cellular homeostasis. Evidence has shown a role for autophagy in tumor cell survival, but the molecular determinants that define sensitivity against autophagic regulation in cancers are not clear. Importantly, we found that breast cancer cells with low expression levels of a zinc-finger protein, ZNF143 (MCF7 sh-ZNF143), showed better survival than control cells (MCF7 sh-Control) under starvation, which was compromised with chloroquine, an autophagy inhibitor. In addition, there were more autophagic vesicles in MCF7 sh-ZNF143 cells than in MCF7 sh-Control cells, and proteins related with the autophagic process, such as Beclin1, p62, and ATGs, were altered in cells with less ZNF143. ZNF143 knockdown affected the stability of p53, which showed a dependence on MG132, a proteasome inhibitor. Data from proteome profiling in breast cancer cells with less ZNF143 suggest a role of NAD(P)H quinone dehydrogenase 1(NQO1) for p53 stability. Taken together, we showed that a subset of breast cancer cells with low expression of ZNF143 might exhibit better survival via an autophagic process by regulating the p53–Beclin1 axis, corroborating the necessity of blocking autophagy for the best therapy.
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DOI: 10.3390/cells8040296
PubMed: 30935019
PubMed Central: 6523662
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Role of ZNF143 in Breast Cancer Cell Survival Through the NAD(P)H Quinone Dehydrogenase 1–p53–Beclin1 Axis Under Metabolic Stress</title><author><name sortKey="Paek, A Rome" sort="Paek, A Rome" uniqKey="Paek A" first="A Rome" last="Paek">A Rome Paek</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation></author><author><name sortKey="Mun, Ji Young" sort="Mun, Ji Young" uniqKey="Mun J" first="Ji Young" last="Mun">Ji Young Mun</name><affiliation><nlm:aff id="af2-cells-08-00296">Department of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu 41068, Korea;<email>jymun@kbri.re.kr</email></nlm:aff></affiliation></author><author><name sortKey="Jo, Mun Jeong" sort="Jo, Mun Jeong" uniqKey="Jo M" first="Mun Jeong" last="Jo">Mun Jeong Jo</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation></author><author><name sortKey="Choi, Hyosun" sort="Choi, Hyosun" uniqKey="Choi H" first="Hyosun" last="Choi">Hyosun Choi</name><affiliation><nlm:aff id="af3-cells-08-00296">BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon 34824, Korea;<email>hyokchoi0123@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Lee, Yun Jeong" sort="Lee, Yun Jeong" uniqKey="Lee Y" first="Yun Jeong" last="Lee">Yun Jeong Lee</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author><author><name sortKey="Cheong, Heesun" sort="Cheong, Heesun" uniqKey="Cheong H" first="Heesun" last="Cheong">Heesun Cheong</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-cells-08-00296">Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408</wicri:regionArea><wicri:noRegion>Gyeonggi 10408</wicri:noRegion></affiliation></author><author><name sortKey="Myung, Jae Kyung" sort="Myung, Jae Kyung" uniqKey="Myung J" first="Jae Kyung" last="Myung">Jae Kyung Myung</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author><author><name sortKey="Hong, Dong Wan" sort="Hong, Dong Wan" uniqKey="Hong D" first="Dong Wan" last="Hong">Dong Wan Hong</name><affiliation><nlm:aff id="af6-cells-08-00296">Bioinformatics Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>dwhong@ncc.re.kr</email> (D.W.H.);<email>jkpark@ncc.re.kr</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Park, Jongkeun" sort="Park, Jongkeun" uniqKey="Park J" first="Jongkeun" last="Park">Jongkeun Park</name><affiliation><nlm:aff id="af6-cells-08-00296">Bioinformatics Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>dwhong@ncc.re.kr</email> (D.W.H.);<email>jkpark@ncc.re.kr</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Kyung Hee" sort="Kim, Kyung Hee" uniqKey="Kim K" first="Kyung-Hee" last="Kim">Kyung-Hee Kim</name><affiliation><nlm:aff id="af7-cells-08-00296">Proteogenomic Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>kyunghee@ncc.re.kr</email></nlm:aff></affiliation></author><author><name sortKey="You, Hye Jin" sort="You, Hye Jin" uniqKey="You H" first="Hye Jin" last="You">Hye Jin You</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30935019</idno><idno type="pmc">6523662</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523662</idno><idno 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Dehydrogenase 1–p53–Beclin1 Axis Under Metabolic Stress</title><author><name sortKey="Paek, A Rome" sort="Paek, A Rome" uniqKey="Paek A" first="A Rome" last="Paek">A Rome Paek</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation></author><author><name sortKey="Mun, Ji Young" sort="Mun, Ji Young" uniqKey="Mun J" first="Ji Young" last="Mun">Ji Young Mun</name><affiliation><nlm:aff id="af2-cells-08-00296">Department of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu 41068, Korea;<email>jymun@kbri.re.kr</email></nlm:aff></affiliation></author><author><name sortKey="Jo, Mun Jeong" sort="Jo, Mun Jeong" uniqKey="Jo M" first="Mun Jeong" last="Jo">Mun Jeong Jo</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation></author><author><name sortKey="Choi, Hyosun" sort="Choi, Hyosun" uniqKey="Choi H" first="Hyosun" last="Choi">Hyosun Choi</name><affiliation><nlm:aff id="af3-cells-08-00296">BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon 34824, Korea;<email>hyokchoi0123@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Lee, Yun Jeong" sort="Lee, Yun Jeong" uniqKey="Lee Y" first="Yun Jeong" last="Lee">Yun Jeong Lee</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author><author><name sortKey="Cheong, Heesun" sort="Cheong, Heesun" uniqKey="Cheong H" first="Heesun" last="Cheong">Heesun Cheong</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af5-cells-08-00296">Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408</wicri:regionArea><wicri:noRegion>Gyeonggi 10408</wicri:noRegion></affiliation></author><author><name sortKey="Myung, Jae Kyung" sort="Myung, Jae Kyung" uniqKey="Myung J" first="Jae Kyung" last="Myung">Jae Kyung Myung</name><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author><author><name sortKey="Hong, Dong Wan" sort="Hong, Dong Wan" uniqKey="Hong D" first="Dong Wan" last="Hong">Dong Wan Hong</name><affiliation><nlm:aff id="af6-cells-08-00296">Bioinformatics Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>dwhong@ncc.re.kr</email> (D.W.H.);<email>jkpark@ncc.re.kr</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Park, Jongkeun" sort="Park, Jongkeun" uniqKey="Park J" first="Jongkeun" last="Park">Jongkeun Park</name><affiliation><nlm:aff id="af6-cells-08-00296">Bioinformatics Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>dwhong@ncc.re.kr</email> (D.W.H.);<email>jkpark@ncc.re.kr</email> (J.P.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Kyung Hee" sort="Kim, Kyung Hee" uniqKey="Kim K" first="Kyung-Hee" last="Kim">Kyung-Hee Kim</name><affiliation><nlm:aff id="af7-cells-08-00296">Proteogenomic Analysis Team, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>kyunghee@ncc.re.kr</email></nlm:aff></affiliation></author><author><name sortKey="You, Hye Jin" sort="You, Hye Jin" uniqKey="You H" first="Hye Jin" last="You">Hye Jin You</name><affiliation><nlm:aff id="af1-cells-08-00296">Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>arpaek@ncc.re.kr</email> (A.R.P.);<email>cromanyon@naver.com</email> (M.J.J.)</nlm:aff></affiliation><affiliation><nlm:aff id="af4-cells-08-00296">Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 10408, Korea;<email>74424@ncc.re.kr</email> (Y.J.L.);<email>heesunch@ncc.re.kr</email> (H.C.);<email>jkmyung@ncc.re.kr</email> (J.K.M.)</nlm:aff></affiliation></author></analytic><series><title level="j">Cells</title><idno type="eISSN">2073-4409</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>Autophagy is a cellular process that disrupts and uses unnecessary or malfunctioning components for cellular homeostasis. Evidence has shown a role for autophagy in tumor cell survival, but the molecular determinants that define sensitivity against autophagic regulation in cancers are not clear. Importantly, we found that breast cancer cells with low expression levels of a zinc-finger protein, ZNF143 (MCF7 sh-ZNF143), showed better survival than control cells (MCF7 sh-Control) under starvation, which was compromised with chloroquine, an autophagy inhibitor. In addition, there were more autophagic vesicles in MCF7 sh-ZNF143 cells than in MCF7 sh-Control cells, and proteins related with the autophagic process, such as Beclin1, p62, and ATGs, were altered in cells with less ZNF143. ZNF143 knockdown affected the stability of p53, which showed a dependence on MG132, a proteasome inhibitor. Data from proteome profiling in breast cancer cells with less ZNF143 suggest a role of NAD(P)H quinone dehydrogenase 1(NQO1) for p53 stability. Taken together, we showed that a subset of breast cancer cells with low expression of ZNF143 might exhibit better survival via an autophagic process by regulating the p53–Beclin1 axis, corroborating the necessity of blocking autophagy for the best therapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Heng, Y J" uniqKey="Heng Y">Y.J. Heng</name></author><author><name sortKey="Lester, S C" uniqKey="Lester S">S.C. Lester</name></author><author><name sortKey="Tse, G M" uniqKey="Tse G">G.M. Tse</name></author><author><name sortKey="Factor, R E" uniqKey="Factor R">R.E. Factor</name></author><author><name sortKey="Allison, K H" uniqKey="Allison K">K.H. Allison</name></author><author><name sortKey="Collins, L C" uniqKey="Collins L">L.C. Collins</name></author><author><name sortKey="Chen, Y Y" uniqKey="Chen Y">Y.Y. Chen</name></author><author><name sortKey="Jensen, K C" uniqKey="Jensen K">K.C. 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Harper</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country></list><tree><noCountry><name sortKey="Choi, Hyosun" sort="Choi, Hyosun" uniqKey="Choi H" first="Hyosun" last="Choi">Hyosun Choi</name><name sortKey="Hong, Dong Wan" sort="Hong, Dong Wan" uniqKey="Hong D" first="Dong Wan" last="Hong">Dong Wan Hong</name><name sortKey="Jo, Mun Jeong" sort="Jo, Mun Jeong" uniqKey="Jo M" first="Mun Jeong" last="Jo">Mun Jeong Jo</name><name sortKey="Kim, Kyung Hee" sort="Kim, Kyung Hee" uniqKey="Kim K" first="Kyung-Hee" last="Kim">Kyung-Hee Kim</name><name sortKey="Lee, Yun Jeong" sort="Lee, Yun Jeong" uniqKey="Lee Y" first="Yun Jeong" last="Lee">Yun Jeong Lee</name><name sortKey="Mun, Ji Young" sort="Mun, Ji Young" uniqKey="Mun J" first="Ji Young" last="Mun">Ji Young Mun</name><name sortKey="Myung, Jae Kyung" sort="Myung, Jae Kyung" uniqKey="Myung J" first="Jae Kyung" last="Myung">Jae Kyung Myung</name><name sortKey="Paek, A Rome" sort="Paek, A Rome" uniqKey="Paek A" first="A Rome" last="Paek">A Rome Paek</name><name sortKey="Park, Jongkeun" sort="Park, Jongkeun" uniqKey="Park J" first="Jongkeun" last="Park">Jongkeun Park</name><name sortKey="You, Hye Jin" sort="You, Hye Jin" uniqKey="You H" first="Hye Jin" last="You">Hye Jin You</name></noCountry><country name="Corée du Sud"><noRegion><name sortKey="Cheong, Heesun" sort="Cheong, Heesun" uniqKey="Cheong H" first="Heesun" last="Cheong">Heesun Cheong</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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