Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity
- Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
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 HIF1α-dependent, with HIF1α integrating signals from PDGFRs and oxygen tension. Inhibition of PDGFR signaling reduces HIF1α half-life, despite buffering of steady-state protein levels by a compensatory increase in HIF1α mRNA. This markedly changes HIF1α protein pool dynamics, and consequently reduces the HIF1α transcriptome. As autocrine growth factor signaling is a hallmark of many cancers, cell-autonomous enhancement of HIF1α-mediated macroautophagy may represent a mechanism for augmenting tumor cell survival under hypoxic conditions.
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Footnotes
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↵1 Corresponding author.
E-MAIL k.ryan{at}beatson.gla.ac.uk; FAX 44-141-942-6521.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.521709.
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Supplemental material is available at http://www.genesdev.org.
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- Received January 9, 2009.
- Accepted April 14, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
