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TRPM7 overexpression enhances the cancer stem cell-like and metastatic phenotypes of lung cancer through modulation of the Hsp90?/uPA/MMP2 signaling pathway #MMPMID30477473
Liu K; Xu SH; Chen Z; Zeng QX; Li ZJ; Chen ZM
BMC Cancer 2018[]; 18 (ä): ä PMID30477473show ga
Background: Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells. Methods: We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines. Results: Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90?, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90?/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p?=?0.007), positive lymph node metastasis (p?=?0.005) and disease grade (p?=?0.003). Conclusions: Through its ability to inhibit Hsp90?/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer. Electronic supplementary material: The online version of this article (10.1186/s12885-018-5050-x) contains supplementary material, which is available to authorized users.