| First Author | Simpson JE | Year | 2024 |
| Journal | Dev Cell | Volume | 59 |
| Issue | 2 | Pages | 228-243.e7 |
| PubMed ID | 38113891 | Mgi Jnum | J:344961 |
| Mgi Id | MGI:7578712 | Doi | 10.1016/j.devcel.2023.11.023 |
| Citation | Simpson JE, et al. (2024) Autophagy supports PDGFRA-dependent brain tumor development by enhancing oncogenic signaling. Dev Cell 59(2):228-243.e7 |
| abstractText | Autophagy 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. |
