Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition
Targeting MEX3A attenuates metastasis of breast cancer via β-catenin signaling pathway inhibition
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靶向 MEX3A 通过抑制 β-catenin 信号通路来减弱乳腺癌的转移
DOI：
10.1016/j.canlet.2021.08.022
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发表时间：
2021-08-24
期刊：
影响因子：
9.7
通讯作者：
Zhu, Chengming
中科院分区：
文献类型：
--
作者：
Wang, Yun;Liang, Qian;Zhu, Chengming
转移是乳腺癌患者死亡的主要原因。了解乳腺癌的转移机制以指导临床诊断和治疗仍然是一个挑战。我们发现Mex-3 RNA结合家族成员A（MEX 3A）在乳腺癌中的表达显著上调，并与肿瘤分级相关。体内外研究结果表明，MEX 3A基因的敲低抑制了乳腺癌细胞的转移，并削弱了乳腺癌细胞的干细胞性。此外，发现β-连环蛋白信号通路的激活是MEX 3A介导的调节的分子中间体。我们还发现，当MEX 3A耗尽时，β-连环蛋白的异位表达恢复了MDAMB-231和BT549细胞的迁移能力、侵袭能力和CD 44（+）/CD 24（-）百分比。此外，我们发现MEX 3A通过下调Dickkopf WNT信号通路抑制剂1（DKK 1）的表达来正向调节β-连环蛋白的表达。因此，在本研究中证明了MEX 3A的先前未发现的作用，其包括通过Wnt/β-连环蛋白途径促进转移和维持乳腺癌的干性的关键贡献。
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 beta-catenin signaling pathway was discovered as a molecular intermediate of MEX3A-mediated regulation. We also found that ectopic expression of beta-catenin restored the migration ability, invasion ability, and CD44(+)/CD24(-) percentage of MDAMB-231 and BT549 cells when MEX3A was depleted. In addition, we revealed that MEX3A positively regulated the expression of beta-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/beta-catenin pathway was demonstrated in the present study.