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Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT)...

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Autores principales: Wu, Deng-Pan, Zhou, Yan, Hou, Li-Xiang, Zhu, Xiao-Xiao, Yi, Wen, Yang, Si-Man, Lin, Tian-Yu, Huang, Jin-Lan, Zhang, Bei, Yin, Xiao-Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315014/
https://www.ncbi.nlm.nih.gov/pubmed/34326682
http://dx.doi.org/10.7150/ijbs.55453
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author Wu, Deng-Pan
Zhou, Yan
Hou, Li-Xiang
Zhu, Xiao-Xiao
Yi, Wen
Yang, Si-Man
Lin, Tian-Yu
Huang, Jin-Lan
Zhang, Bei
Yin, Xiao-Xing
author_facet Wu, Deng-Pan
Zhou, Yan
Hou, Li-Xiang
Zhu, Xiao-Xiao
Yi, Wen
Yang, Si-Man
Lin, Tian-Yu
Huang, Jin-Lan
Zhang, Bei
Yin, Xiao-Xing
author_sort Wu, Deng-Pan
collection PubMed
description Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.
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spelling pubmed-83150142021-07-28 Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway Wu, Deng-Pan Zhou, Yan Hou, Li-Xiang Zhu, Xiao-Xiao Yi, Wen Yang, Si-Man Lin, Tian-Yu Huang, Jin-Lan Zhang, Bei Yin, Xiao-Xing Int J Biol Sci Research Paper Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance. Ivyspring International Publisher 2021-06-11 /pmc/articles/PMC8315014/ /pubmed/34326682 http://dx.doi.org/10.7150/ijbs.55453 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wu, Deng-Pan
Zhou, Yan
Hou, Li-Xiang
Zhu, Xiao-Xiao
Yi, Wen
Yang, Si-Man
Lin, Tian-Yu
Huang, Jin-Lan
Zhang, Bei
Yin, Xiao-Xing
Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title_full Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title_fullStr Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title_full_unstemmed Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title_short Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway
title_sort cx43 deficiency confers emt-mediated tamoxifen resistance to breast cancer via c-src/pi3k/akt pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315014/
https://www.ncbi.nlm.nih.gov/pubmed/34326682
http://dx.doi.org/10.7150/ijbs.55453
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