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

Azimi, Iman, Milevskiy, Michael J. G., Kaemmerer, Elke, Turner, Dane, Yapa, Kunsala T. D. S., Brown, Melissa A., Thompson, Erik W., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2017) TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells. Journal of Cell Science, 130 14: 2292-2305. doi:10.1242/jcs.196659

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Author Azimi, Iman
Milevskiy, Michael J. G.
Kaemmerer, Elke
Turner, Dane
Yapa, Kunsala T. D. S.
Brown, Melissa A.
Thompson, Erik W.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
0021-9533
Publication date 2017-07-01
Year available 2017
Sub-type Article (original research)
DOI 10.1242/jcs.196659
Open Access Status File (Publisher version)
Volume 130
Issue 14
Start page 2292
End page 2305
Total pages 14
Place of publication Cambridge, United Kingdom
Publisher Company of Biologists
Language eng
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 metastasisrelated 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.
Keyword Akt
Breast cancer
Ca2+
Hypoxia
PTEN
Signal transduction
TRPC1
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 569645
1042819
CG-10-04
CG-12-07
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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