TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

• DOI: 10.1242/jcs.196659
• Publication Date: 2017-05-31T00:10:22Z
• Authors: Iman Azimi; Michael J. G. Mil...; Elke Kaemmerer; Dane Turner; Kunsala T. D. S. ...; Melissa A. Brown; Erik W. Thompson; Sarah J. Roberts-...; Gregory R. Monteith
• Keywords: Hypoxia

Hypoxia is a feature of the tumour microenvironment that promotes invasiveness, resistance to chemotherapeutics and cell survival. Our studies identify transient receptor potential canonical-1 (TRPC1) ion channel as key component responses hypoxia in breast cancer cells. This regulation includes control specific epithelial mesenchymal transition (EMT) events hypoxia-mediated activation signalling pathways such EGFR, STAT3 autophagy marker LC3B, through hypoxia-inducible factor-1α (HIF1α)-dependent -independent mechanisms. TRPC1 regulated HIF1α levels PTEN-deficient MDA-MB-468 HCC1569 lines. arises from effects on constitutive translation under normoxic conditions via an Akt-dependent pathway. In further support role EMT, its expression closely associated with EMT- metastasis-related genes tumours, enhanced basal B also significantly prognostic for cancers, particularly those classified lymph node positive. The defined roles identified here could be therapeutically exploited oncogenic