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

Simon Wilkinson, Jim O'Prey, Michael Fricker, Kevin M Ryan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 HIF1alpha-dependent, with HIF1alpha integrating signals from PDGFRs and oxygen tension. Inhibition of PDGFR signaling reduces HIF1alpha half-life, despite buffering of steady-state protein levels by a compensatory increase in HIF1alpha mRNA. This markedly changes HIF1alpha protein pool dynamics, and consequently reduces the HIF1alpha transcriptome. As autocrine growth factor signaling is a hallmark of many cancers, cell-autonomous enhancement of HIF1alpha-mediated macroautophagy may represent a mechanism for augmenting tumor cell survival under hypoxic conditions.
Original languageEnglish
Pages (from-to)1283-8
Number of pages6
JournalGenes & Development
Volume23
Issue number11
DOIs
Publication statusPublished - 2009

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