Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition

Yun Wang; Qian Liang; Kefeng Lei; Qingqing Zhu; Delong Zeng; Yuhong Liu; Yingsi Lu; Tingting Kang; Nannan Tang; Lifen Huang; Liping Ye; Di Tang; Chengming Zhu

doi:10.1016/j.canlet.2021.08.022

Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition

Cancer Lett. 2021 Aug 21:521:50-63. doi: 10.1016/j.canlet.2021.08.022. Online ahead of print.

Authors

Yun Wang¹, Qian Liang¹, Kefeng Lei², Qingqing Zhu¹, Delong Zeng³, Yuhong Liu², Yingsi Lu¹, Tingting Kang¹, Nannan Tang⁴, Lifen Huang⁴, Liping Ye¹, Di Tang², Chengming Zhu⁵

Affiliations

¹ Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
² Department of General Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
³ Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.
⁴ Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁵ Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: zhuchm3@mail.sysu.edu.cn.

PMID: 34425185
DOI: 10.1016/j.canlet.2021.08.022

Abstract

Metastasis is the major cause of mortality in patients with breast cancer. Understanding the metastatic mechanism to guide clinical diagnoses and the treatment of breast cancer remains a challenge. We found that the expression of Mex-3 RNA binding family member A (MEX3A) was upregulated significantly and related to tumor grade in breast cancer. The results of in vitro and in vivo studies showed that knockdown of MEX3A inhibited the metastasis and impaired the stemness of breast cancer cells. Furthermore, activation of the β-catenin signaling pathway was discovered as a molecular intermediate of MEX3A-mediated regulation. We also found that ectopic expression of β-catenin restored the migration ability, invasion ability, and CD44⁺/CD24^- percentage of MDA-MB-231 and BT549 cells when MEX3A was depleted. In addition, we revealed that MEX3A positively regulated the expression of β-catenin by downregulating Dickkopf WNT signaling pathway inhibitor 1 (DKK1) expression. Therefore, a previously undiscovered role of MEX3A comprising a critical contribution to promoting metastasis and maintaining the stemness of breast cancer via the Wnt/β-catenin pathway was demonstrated in the present study.

Keywords: Breast cancer; DKK1; MEX3A; Metastasis; Wnt/β-catenin.