TRPC1 regulates hypoxia associated events in PTEN-deficient breast cancer cells

TRPC1 was the first member of the non-selective cation transient receptor potential (TRP) ion channel family identified in mammals; however the exact physiological function of TRPC1 as a channel is still not fully understood. TRPC1 knockout mice have been previously described as not having "dramatic" phenotypes. Our unpublished studies identified the TRPC1 ion channel as an integral player of responses to hypoxia, a hallmark of the tumour microenvironment in breast cancer cells, that promotes invasiveness and resistance to chemotherapeutics. TRPC1 was involved in the regulation of specific markers of hypoxia-induced epithelial to mesenchymal transition (EMT), as well as activation of EGFR and STAT3 signalling. TRPC1 also played a role in the regulation of constitutive levels of HIF1α in an Akt-dependent manner in PTEN-deficient MDA-MB-468 and HCC1569 breast cancer cell lines. Furthermore, we identified a close association between the expression of TRPC1 with EMT and metastasis-related genes in breast tumours, as well as survival in basal breast cancer patients. This study presents TRPC1 as a potential therapeutic target for the control of breast cancer metastasis.