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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Ryan, Professor Kevin and Wilkinson, Dr Simon 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 > School of Cancer Sciences |
Journal Name: | Genes and Development |
ISSN: | 0890-9369 |
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