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

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	Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer
	Zhao, P; Sun, J; Huang, XW; Zhang, XW; Liu, X; Liu, R; Du, GS; Gan, WQ; Yang, CY; Tang, YY; Chen, CS; Jiang, DW
	2023
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
ISSN	1449-2288
卷号	19 期号:6 页码:1861-1874
摘要	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-alpha could promote BLBC cell stemness partially by activating the KLF5-EphA2 axis. Moreover, phosphorylation of EphA2 at S897 (EphA2 pS897) induced by TNF-alpha 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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14192
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Zhao, P,Sun, J,Huang, XW,et al. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023,19(6):1861-1874.
APA	Zhao, P.,Sun, J.,Huang, XW.,Zhang, XW.,Liu, X.,...&Jiang, DW.(2023).Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19(6),1861-1874.
MLA	Zhao, P,et al."Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19.6(2023):1861-1874.

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