Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition. (28th November 2021)

• Record Type: Journal Article
• Authors: Wang, Yun; Liang, Qian; Lei, Kefeng; Zhu, Qingqing; Zeng, Delong; Liu, Yuhong; Lu, Yingsi; Kang, Tingting; Tang, Nannan; Huang, Lifen; Ye, Liping; Tang, Di; Zhu, Chengming
• Is Part Of: Cancer letters. Volume 521(2021)
• Page Start: 50
• Page End: 63
• Publication Date: 2021-11-28
• Subjects: MEX3A -- Breast cancer -- Wnt/β-catenin -- DKK1 -- Metastasis; MEX3A Mex-3 RNA Binding Family Member A -- CSCs Cancer Stem Cells -- MiRISC microRNA-induced silencing complex -- CDX2 Caudal Type Homeobox 2 -- RIG-I Retinoic acid-Inducible Gene I -- RBPs RNA Binding proteins -- SAM68 Src-associated in mitosis 68 kDa protein -- DKK1 Dickkopf WNT Signaling Pathway Inhibitor 1 -- SRSF1 serine and arginine rich splicing factor 1 -- HuR Hu antigen R -- PEI polyethylenimine -- bFGF basic Fibroblast Growth Factor -- EGF Epidermal Growth Factor -- SOX2 encoding SRY-box transcription factor 2 -- POU5F1 POU Class 5 homeobox 1 -- NANOG Nanog homeobox -- PROM1 Prominin 1 -- BTRC beta-transducin repeat containing E3 ubiquitin protein ligase -- FBXW2 F-box and WD repeat domain containing 2 -- HUWE1 HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 -- SKP2 S-phase kinase associated protein 2; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.08.022
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: MEX3A was found upregulated in breast cancer and its expression level was corelated with tumor grade. Inhibition of MEX3A reduced metastatic potential and stemness of breast cancer cells. MEX3A promoted degradation of DKK1 mRNA to activate Wnt/β-catenin signaling, thus fueled breast cancer metastasis.