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Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation
Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long‐ter...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982582/ https://www.ncbi.nlm.nih.gov/pubmed/36581470 http://dx.doi.org/10.1002/advs.202202956 |
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author | Li, Jiang Xia, Qidong Di, Can Li, Chunni Si, Hang Zhou, Boxuan Yu, Shubin Li, Yihong Huang, Jingying Lu, Yiwen Huang, Min Liang, Huixin Liu, Xinwei Zhao, Qiyi |
author_facet | Li, Jiang Xia, Qidong Di, Can Li, Chunni Si, Hang Zhou, Boxuan Yu, Shubin Li, Yihong Huang, Jingying Lu, Yiwen Huang, Min Liang, Huixin Liu, Xinwei Zhao, Qiyi |
author_sort | Li, Jiang |
collection | PubMed |
description | Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long‐term prognosis in these patients. The CD96(+) cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell‐intrinsic CD96 enhances the chemotherapeutic response in a patient‐derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid β‐oxidation via the CD155‐CD96‐Src‐Stat3‐Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell‐intrinsic CD96 and an attractive target in improving the chemotherapeutic response. |
format | Online Article Text |
id | pubmed-9982582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99825822023-03-04 Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation Li, Jiang Xia, Qidong Di, Can Li, Chunni Si, Hang Zhou, Boxuan Yu, Shubin Li, Yihong Huang, Jingying Lu, Yiwen Huang, Min Liang, Huixin Liu, Xinwei Zhao, Qiyi Adv Sci (Weinh) Research Articles Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long‐term prognosis in these patients. The CD96(+) cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell‐intrinsic CD96 enhances the chemotherapeutic response in a patient‐derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid β‐oxidation via the CD155‐CD96‐Src‐Stat3‐Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell‐intrinsic CD96 and an attractive target in improving the chemotherapeutic response. John Wiley and Sons Inc. 2022-12-29 /pmc/articles/PMC9982582/ /pubmed/36581470 http://dx.doi.org/10.1002/advs.202202956 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Li, Jiang Xia, Qidong Di, Can Li, Chunni Si, Hang Zhou, Boxuan Yu, Shubin Li, Yihong Huang, Jingying Lu, Yiwen Huang, Min Liang, Huixin Liu, Xinwei Zhao, Qiyi Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title | Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title_full | Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title_fullStr | Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title_full_unstemmed | Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title_short | Tumor Cell‐Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β‐Oxidation |
title_sort | tumor cell‐intrinsic cd96 mediates chemoresistance and cancer stemness by regulating mitochondrial fatty acid β‐oxidation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982582/ https://www.ncbi.nlm.nih.gov/pubmed/36581470 http://dx.doi.org/10.1002/advs.202202956 |
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