Article ; Online: TRPM7 overexpression enhances the cancer stem cell-like and metastatic phenotypes of lung cancer through modulation of the Hsp90α/uPA/MMP2 signaling pathway.
BMC cancer
2018 Volume 18, Issue 1, Page(s) 1167
Abstract: ... A on CSCs-like and metastatic lung cancer cells.: Methods: We demonstrated and compared TRPM7 expression ... markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin ... to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is ...
| Abstract | 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, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/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 Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer. |
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| MeSH term(s) | Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Matrix Metalloproteinase 2/metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism ; Phenotype ; Prognosis ; Protein Kinase Inhibitors/pharmacology ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/genetics ; Signal Transduction ; TRPM Cation Channels/antagonists & inhibitors ; TRPM Cation Channels/genetics |
| Chemical Substances | HSP90 Heat-Shock Proteins ; HSP90AA2P protein, human ; Protein Kinase Inhibitors ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) |
| Language | English |
| Publishing date | 2018-11-26 |
| Publishing country | England |
| Document type | Journal Article |
| ISSN | 1471-2407 |
| ISSN (online) | 1471-2407 |
| DOI | 10.1186/s12885-018-5050-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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