Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity

Wilkinson, S., O'Prey, J., Fricker, M. and Ryan, K.M. (2009) Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity. Genes and Development, 23(11), pp. 1283-1288. (doi:10.1101/gad.521709)

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Publisher's URL: http://dx.doi.org/10.1101/gad.521709

Abstract

The selective regulation of macroautophagy remains poorly defined. Here we report that PDGFR signaling is an essential selective promoter of hypoxia-induced macroautophagy. Hypoxia-induced macroautophagy in tumor cells is also HIF1 alpha-dependent, with HIF1 alpha integrating signals from PDGFRs and oxygen tension. Inhibition of PDGFR signaling reduces HIF1 alpha half-life, despite buffering of steady-state protein levels by a compensatory increase in HIF1 alpha mRNA. This markedly changes HIF1 alpha protein pool dynamics, and consequently reduces the HIF1 alpha transcriptome. As autocrine growth factor signaling is a hallmark of many cancers, cell-autonomous enhancement of HIF1 alpha-mediated macroautophagy may represent a mechanism for augmenting tumor cell survival under hypoxic conditions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkinson, Dr Simon and Ryan, Professor Kevin and O'Prey, Mr James and Fricker, Mr Michael
Authors: Wilkinson, S., O'Prey, J., Fricker, M., and Ryan, K.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Genes and Development
ISSN:0890-9369

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