CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway

Tao Dai; Yiqi Liu; Renxian Cao; Jingying Cao

doi:10.1016/j.tranon.2022.101468

CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway

Transl Oncol. 2022 Oct:24:101468. doi: 10.1016/j.tranon.2022.101468. Epub 2022 Jul 14.

Authors

Tao Dai¹, Yiqi Liu², Renxian Cao³, Jingying Cao⁴

Affiliations

¹ Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha 410013 Hunan Province, PR China.
² The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
³ Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
⁴ Department of Medicine Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan Province, PR China. Electronic address: caojingying1202@hotmail.com.

Abstract

Background: Basal-like breast cancer (BLBC) is an important subtype of breast cancer. Twist1 is a key transcription factor in BLBC metastasis, which serves a key role in tumorigenesis. The potential mechanism of Twist1 in BLBC remains to be elucidated. Here, we explored the role and molecular mechanism of Twist1 in BLBC.

Methods: The levels of CBX7, Twist1 and EphA2 in BLBC tissues and cells were determined by Western blot. ChIP and dual-luciferase reporter assays confirmed the interaction between CBX7, Twist1 and EphA2 promoter. The cellular functions were analyzed by CCK-8, colony formation, wound healing and Transwell assays. Expression of EMT related proteins was analyzed by Western blot. IHC measured the expression of CBX7, Twist1 and EphA2 in tumor tissues.

Results: CBX7 was down-regulated in BLBC tissues and cells, whereas Twist1 and EphA2 were up-regulated. Twist1 silencing inhibited the cell migration, invasion and cancer metastasis of BLBC through targeting EphA2 and regulating EphA2 expression. Additionally, CBX7 blocked the binding of Twist1 to EphA2 promoter and inhibited EphA2 expression and suppressed BLBC growth and metastasis via Twist1/EphA2 axis.

Conclusion: CBX7 suppresses BLBC growth and metastasis through Twist1/EphA2 pathway. Our study may provide evidence and new therapeutic targets for the comprehensive treatment of BLBC.

Keywords: Basal-like breast cancer; CBX7; EphA2; Metastasis; Twist1.