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Int J Biol Sci 2023; 19(6):1861-1874. doi:10.7150/ijbs.82567 This issue Cite

Research Paper

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

Ping Zhao1#, Jian Sun1#, Xinwei Huang2#, Xiangwu Zhang1, Xin Liu1, Rong Liu3, Guangshi Du4, Wenqiang Gan5,6, Chuanyu Yang5, Yiyin Tang1✉, Ceshi Chen1,5,7✉, Dewei Jiang5,6✉

1. The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
2. Key Laboratory of The Second Affiliated Hospital of Kuming Medical College, Kunming, 650101, China
3. Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034 China
4. Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550025 China
5. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 China
6. Kunming College of Life Sciences, University of the Chinese Academy of Sciences, Kunming, 650204 China
7. Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500 China
# Equal contribution

✉ Corresponding authors: Dewei Jiang, jiangdeweikiz.ac.cn, orcid.org/0000-0002-7773-5449; Ceshi Chen, chencedu.cn, orcid.org/0000-0001-6398-3516; Yiying Tang, tyy1485com

Citation:
Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, Du G, Gan W, Yang C, Tang Y, Chen C, Jiang D. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci 2023; 19(6):1861-1874. doi:10.7150/ijbs.82567. https://www.ijbs.com/v19p1861.htm
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Abstract

Graphic abstract

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.

Keywords: EphA2, TNF-α, KLF5, BLBC stem cells, Chemoresistance, ALW-II-41-27

Citation styles

APA
Zhao, P., Sun, J., Huang, X., Zhang, X., Liu, X., Liu, R., Du, G., Gan, W., Yang, C., Tang, Y., Chen, C., Jiang, D. (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. https://doi.org/10.7150/ijbs.82567.

ACS
Zhao, P.; Sun, J.; Huang, X.; Zhang, X.; Liu, X.; Liu, R.; Du, G.; Gan, W.; Yang, C.; Tang, Y.; Chen, C.; Jiang, D. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int. J. Biol. Sci. 2023, 19 (6), 1861-1874. DOI: 10.7150/ijbs.82567.

NLM
Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, Du G, Gan W, Yang C, Tang Y, Chen C, Jiang D. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci 2023; 19(6):1861-1874. doi:10.7150/ijbs.82567. https://www.ijbs.com/v19p1861.htm

CSE
Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, Du G, Gan W, Yang C, Tang Y, Chen C, Jiang D. 2023. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci. 19(6):1861-1874.

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