2. Academic Validation
  3. Autophagy supports PDGFRA-dependent brain tumor development by enhancing oncogenic signaling

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.
Joanne E Simpson 1,  Morwenna T Muir 1,  Martin Lee 1,  Catherine Naughton 2,  Nick Gilbert 2,  Steven M Pollard 3,  Noor Gammoh 4
Affiliations

Affiliations

  • 1 Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
  • 2 MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK.
  • 3 Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.
  • 4 Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK. Electronic address: noor.gammoh@ed.ac.uk.
PMID: 38113891 DOI: 10.1016/j.devcel.2023.11.023
Abstract

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.

Keywords

PDGFRA; PTEN; RTK; autophagy; cancer; endocytosis; glioblastoma; signaling.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z