mortalin通过激活Wnt/GSK3β/β-连环蛋白信号通路维持乳腺癌干细胞的干性。
Mortalin maintains breast cancer stem cells stemness via activation of Wnt/GSK3β/β-catenin signaling pathway.
作者信息
Wei Bo, Cao Jia, Tian Jin-Hai, Yu Chuan-Yang, Huang Qi, Yu Jing-Jing, Ma Rong, Wang Jia, Xu Fang, Wang Li-Bin
机构信息
The General Hospital of Ningxia Medical University Yinchuan 750004, China.
Ningxia Medical University Yinchuan 750004, China.
出版信息
Am J Cancer Res. 2021 Jun 15;11(6):2696-2716. eCollection 2021.
Previous research indicated that mortalin overexpressed in breast cancer and contributed to carcinogenesis. Mortalin was also demonstrated to promote Epithelial-mesenchymal transition (EMT) and was considered as a factor for maintaining the stemness of the cancer stem cells. However, the underlying mechanisms about mortalin maintaining the stemness of breast cancer stem cells (BCSCs) remain unclear. Here, we identified that increased expression of mortalin in breast cancer was associated with poorer overall survival rate. Mortalin was elevated in breast cancer cell lines and BCSC-enriched populations. Additionally, knockdown of mortalin significantly inhibited the cell proliferation, migration and EMT, as well as sphere forming capacity and stemness genes expression. Further study revealed that mortalin promoted EMT and maintained BCSCs stemness via activating the Wnt/GSK3β/β-catenin signaling pathway and . Taken together, these findings unveiled the mechanism of mortalin in maintaining and regulating the stemness of BCSCs, and may offer novel therapeutic strategies for breast cancer treatment.
先前的研究表明，mortalin在乳腺癌中过表达并促进致癌作用。mortalin还被证明可促进上皮-间质转化（EMT），并被认为是维持癌症干细胞干性的一个因素。然而，mortalin维持乳腺癌干细胞（BCSCs）干性的潜在机制仍不清楚。在此，我们发现乳腺癌中mortalin表达增加与较差的总生存率相关。mortalin在乳腺癌细胞系和富含BCSC的群体中升高。此外，敲低mortalin可显著抑制细胞增殖、迁移和EMT，以及球体形成能力和干性基因表达。进一步研究表明，mortalin通过激活Wnt/GSK3β/β-连环蛋白信号通路促进EMT并维持BCSCs的干性。综上所述，这些发现揭示了mortalin在维持和调节BCSCs干性方面的机制，并可能为乳腺癌治疗提供新的治疗策略。
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