Drug Discov Ther. 2025;19(5):325-336. (DOI: 10.5582/ddt.2025.01082)
TRPC6 expression is negatively correlated with breast cancer progression
Ma YF, Li GN, Yu HY, Wang BK, Diao ZH, Du Y, Wang HB, Liu HP
The transient receptor potential channel 6 (TRPC6), a Ca2+-permeable, non-selective cation channel, is a potential drug target widely expressed in most human tissues. However, the role of TRPC6 in breast cancer remains largely unknown. We comprehensively investigated the relationships between TRPC6 and breast cancer using online databases, including TIMER, cBioPortal, UALCAN, the Kaplan-Meier plotter, the Human Protein Atlas, STRING, and the LinkedOmics, to evaluate the prognostic value of TRPC6. We also tentatively explored the effects of TRPC6 modulation on proliferation and metastasis potential in several breast cancer cell lines by MTT assay, colony formation assay, flow cytometry, and scratch wound healing assay. The TCGA data showed lower TRPC6 gene expression in breast tumours versus normal breast tissues. The Human Protein Atlas revealed that the TRPC6 protein was generally expressed at low levels in both normal and breast carcinoma tissue. The Kaplan-Meier plotter showed that the low TRPC6 level is correlated with worse relapse-free survival probability in breast cancer. Moreover, the TRPC6 gene was linked to immune infiltration in breast cancer, and this relationship affected the prognosis of breast cancer. In contrast to published researches, we found that TRPC6 expression was negatively correlated with breast cancer cell proliferation and metastasis abilities, suggesting TRPC6 as a promising prognostic biomarker for breast cancer, where low expression of TRPC6 was related to worse prognoses. This research raises the necessity of rethinking the mechanism perspective and targetability of TRPC6 in breast cancer, which warrants further investigation.
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