TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via activating AKT/GSK-3β pathway

• Published in: Tumor biology 2014-09, Vol.35 (9), p.8969-8977
• Main Authors: Liu, Jinxin, Chen, Yizhi, Shuai, Shuai, Ding, Dapeng, Li, Rong, Luo, Rongcheng
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Blotting, Western; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Cell Line; Cell Line, Tumor; Cell Movement - genetics; Epithelial-Mesenchymal Transition; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; MCF-7 Cells; Microscopy, Confocal; Proto-Oncogene Proteins c-akt - metabolism; Research Article; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal Transduction; TRPM Cation Channels - genetics; TRPM Cation Channels - metabolism; Up-Regulation
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2077-8

Breast cancer already taken the first place of incidence in Chinese female cancer patients. TRPM8 is found to be over-expressed in breast cancer, but whether it promotes breast cancer aggressiveness remains unknown. In our study, TRPM8 was identified highly expressing in all the tested breast cancer cell lines including MCF-7, T47D, MDA-MB-231, BT549, SKBR3 and ZR-75-30, while it just could be detected in MCF-10A, the normal breast epithelial cell. Then four pairs of clinical samples were analyzed using Western blotting and the result showed that TRPM8 expression is higher in tumor tissues than in adjacent nontumor tissues. Subsequently, we established TRPM8 high-expressing MCF-7 cell line and TRPM8 knockout MDA-MB-231 cell line to explore expression status of cancer-related proteins. The Western blotting and immunofluorescence analysis outcomes demonstrated that TRPM8 might influence cancer cell metastasis by regulating the EMT phenotype via activating AKT/GSK-3β pathway, and the hypothesis had been supported by cell function tests. All the results demonstrated that TRPM8 significantly up-expressed in breast cancer cells and promoted their metastasis by regulating EMT via activating AKT/GSK-3β pathway, indicating TRPM8 gets the prospects of to be developed as medication or diagnostic indicator to be applied in clinical work.