Oncotarget 2014-10-15

Hypoxia-inducible factors enhance glutamate signaling in cancer cells.

Hongxia Hu, Naoharu Takano, Lisha Xiang, Daniele M Gilkes, Weibo Luo, Gregg L Semenza

Index: Oncotarget 5(19) , 8853-68, (2014)

Full Text: HTML

Abstract

Signaling through glutamate receptors has been reported in human cancers, but the molecular mechanisms are not fully delineated. We report that in hepatocellular carcinoma and clear cell renal carcinoma cells, increased activity of hypoxia-inducible factors (HIFs) due to hypoxia or VHL loss-of-function, respectively, augmented release of glutamate, which was mediated by HIF-dependent expression of the SLC1A1 and SLC1A3 genes encoding glutamate transporters. In addition, HIFs coordinately regulated expression of the GRIA2 and GRIA3 genes, which encode glutamate receptors. Binding of glutamate to its receptors activated SRC family kinases and downstream pathways, which stimulated cancer cell proliferation, apoptosis resistance, migration and invasion in different cancer cell lines. Thus, coordinate regulation of glutamate transporters and receptors by HIFs was sufficient to activate key signal transduction pathways that promote cancer progression.

Related Compounds

  • Isopropanol
  • sulfasalazine

Related Articles:

Genome-wide shRNA screening identifies host factors involved in early endocytic events for HIV-1-induced CD4 down-regulation.

2014-01-01

[Retrovirology 11 , 118, (2015)]

Comparative in vitro study on magnetic iron oxide nanoparticles for MRI tracking of adipose tissue-derived progenitor cells.

2014-01-01

[PLoS ONE 9(9) , e108055, (2014)]

Comparison of the antifungal efficacy of terbinafine hydrochloride and ciclopirox olamine containing formulations against the dermatophyte Trichophyton rubrum in an infected nail plate model.

2014-07-07

[Mol. Pharm. 11(7) , 1991-6, (2014)]

Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations.

2015-02-01

[Cancer Chemother. Pharmacol. 75(2) , 431-7, (2015)]

Use of an enzyme-assisted method to improve protein extraction from olive leaves.

2015-02-15

[Food Chem. 169 , 28-33, (2014)]

More Articles...