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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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