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

Citation

Azimi, I and Milevskiy, MJG and Kaemmerer, E and Turner, D and Yapa, KTDS and Brown, MA and Thompson, EW and Roberts-Thomson, SJ and Monteith, GR, TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells, Journal of Cell Science, 130, (14) pp. 2292-2305. ISSN 0021-9533 (2017) [Refereed Article]


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Copyright 2017 The Authors

DOI: doi:10.1242/jcs.196659

Abstract

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

Item Details

Item Type:Refereed Article
Keywords:TRPC1 is a differential regulator of hypoxia-mediated events and Akt signaling in PTEN-deficient breast cancer cells
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Cell Biology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Azimi, I (Dr Iman Azimi)
ID Code:124402
Year Published:2017
Web of Science® Times Cited:10
Deposited By:Pharmacy
Deposited On:2018-02-21
Last Modified:2018-04-10
Downloads:1 View Download Statistics

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