Autophagy supports PDGFRA-dependent brain tumor development by enhancing oncogenic signaling

Dev Cell. 2023 Dec 8:S1534-5807(23)00621-4. doi: 10.1016/j.devcel.2023.11.023. Online ahead of print.ABSTRACTAutophagy is a conserved cellular degradation process. While autophagy-related proteins were shown to influence the signaling and trafficking of some receptor tyrosine kinases, the relevance of this during cancer development is unclear. Here, we identify a role for autophagy in regulating platelet-derived growth factor receptor alpha (PDGFRA) signaling and levels. We find that PDGFRA can be targeted for autophagic degradation through the activity of the autophagy cargo receptor p62. As a result, short-term autophagy inhibition leads to elevated levels of PDGFRA but an unexpected defect in PDGFA-mediated signaling due to perturbed receptor trafficking. Defective PDGFRA signaling led to its reduced levels during prolonged autophagy inhibition, suggesting a mechanism of adaptation. Importantly, PDGFA-driven gliomagenesis in mice was disrupted when autophagy was inhibited in a manner dependent on Pten status, thus highlighting a genotype-specific role for autophagy during tumorigenesis. In summary, our data provide a mechanism by which cells require autophagy to drive tumor formation.PMID:38113891 | DOI:10.1016/j.devcel.2023.11.023

Source: Developmental Cell - December 19, 2023 Category: Cytology Authors: Joanne E Simpson Morwenna T Muir Martin Lee Catherine Naughton Nick Gilbert Steven M Pollard Noor Gammoh Source Type: research