title: Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity.
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 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.
authors.affiliation: Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkinson
authors.forename: Jim
authors.initials: J
authors.lastname: O'Prey
authors.forename: Michael
authors.initials: M
authors.lastname: Fricker
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D019898:Autocrine Communication; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D000860:Hypoxia; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D017479:Receptors, Platelet-Derived Growth Factor