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Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer

Ephrin type-A receptor 2 (EphA2) is a member of the tyrosine receptor kinases, a family of membrane proteins recognized as potential anticancer targets. EphA2 highly expressed in a variety of human cancers, playing roles in proliferation, migration, and invasion. However, whether and how EphA2 regul...

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Autores principales: Zhao, Ping, Sun, Jian, Huang, Xinwei, Zhang, Xiangwu, Liu, Xin, Liu, Rong, Du, Guangshi, Gan, Wenqiang, Yang, Chuanyu, Tang, Yiyin, Chen, Ceshi, Jiang, Dewei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092769/
https://www.ncbi.nlm.nih.gov/pubmed/37063424
http://dx.doi.org/10.7150/ijbs.82567
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author Zhao, Ping
Sun, Jian
Huang, Xinwei
Zhang, Xiangwu
Liu, Xin
Liu, Rong
Du, Guangshi
Gan, Wenqiang
Yang, Chuanyu
Tang, Yiyin
Chen, Ceshi
Jiang, Dewei
author_facet Zhao, Ping
Sun, Jian
Huang, Xinwei
Zhang, Xiangwu
Liu, Xin
Liu, Rong
Du, Guangshi
Gan, Wenqiang
Yang, Chuanyu
Tang, Yiyin
Chen, Ceshi
Jiang, Dewei
author_sort Zhao, Ping
collection PubMed
description Ephrin type-A receptor 2 (EphA2) is a member of the tyrosine receptor kinases, a family of membrane proteins recognized as potential anticancer targets. EphA2 highly expressed in a variety of human cancers, playing roles in proliferation, migration, and invasion. However, whether and how EphA2 regulates basal-like breast cancer (BLBC) cell stemness and chemoresistance has not been revealed. Here, KLF5 was proven to be a direct transcription factor for EphA2 in BLBC cells, and its expression was positively correlated in clinical samples from breast cancer patients. The inflammatory factor TNF-α could promote BLBC cell stemness partially by activating the KLF5-EphA2 axis. Moreover, phosphorylation of EphA2 at S897 (EphA2 pS897) induced by TNF-α and PTX/DDP contributes to chemoresistance of BLBC. Furthermore, the EphA2 inhibitor ALW-II-41-27 could effectively reduce EphA2 pS897 and tumor cell stemness in vitro and significantly enhance the sensitivity of xenografts to the chemotherapeutic drugs PTX and DDP in vivo. Clinically, tumor samples from breast patients with less response to neoadjuvant chemotherapy showed a high level of EphA2 pS897 expression. In conclusion, KLF5-EphA2 promotes stemness and drug resistance in BLBC and could be a potential target for the treatment of BLBC.
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spelling pubmed-100927692023-04-13 Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer Zhao, Ping Sun, Jian Huang, Xinwei Zhang, Xiangwu Liu, Xin Liu, Rong Du, Guangshi Gan, Wenqiang Yang, Chuanyu Tang, Yiyin Chen, Ceshi Jiang, Dewei Int J Biol Sci Research Paper Ephrin type-A receptor 2 (EphA2) is a member of the tyrosine receptor kinases, a family of membrane proteins recognized as potential anticancer targets. EphA2 highly expressed in a variety of human cancers, playing roles in proliferation, migration, and invasion. However, whether and how EphA2 regulates basal-like breast cancer (BLBC) cell stemness and chemoresistance has not been revealed. Here, KLF5 was proven to be a direct transcription factor for EphA2 in BLBC cells, and its expression was positively correlated in clinical samples from breast cancer patients. The inflammatory factor TNF-α could promote BLBC cell stemness partially by activating the KLF5-EphA2 axis. Moreover, phosphorylation of EphA2 at S897 (EphA2 pS897) induced by TNF-α and PTX/DDP contributes to chemoresistance of BLBC. Furthermore, the EphA2 inhibitor ALW-II-41-27 could effectively reduce EphA2 pS897 and tumor cell stemness in vitro and significantly enhance the sensitivity of xenografts to the chemotherapeutic drugs PTX and DDP in vivo. Clinically, tumor samples from breast patients with less response to neoadjuvant chemotherapy showed a high level of EphA2 pS897 expression. In conclusion, KLF5-EphA2 promotes stemness and drug resistance in BLBC and could be a potential target for the treatment of BLBC. Ivyspring International Publisher 2023-03-21 /pmc/articles/PMC10092769/ /pubmed/37063424 http://dx.doi.org/10.7150/ijbs.82567 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
Zhao, Ping
Sun, Jian
Huang, Xinwei
Zhang, Xiangwu
Liu, Xin
Liu, Rong
Du, Guangshi
Gan, Wenqiang
Yang, Chuanyu
Tang, Yiyin
Chen, Ceshi
Jiang, Dewei
Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title_full Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title_fullStr Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title_full_unstemmed Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title_short Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
title_sort targeting the klf5-epha2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092769/
https://www.ncbi.nlm.nih.gov/pubmed/37063424
http://dx.doi.org/10.7150/ijbs.82567
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