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EGFR and EGFRvIII coopt host defense pathways, promoting progression in glioblastoma

ABSTRACT: Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockdown of TLR2 led to a dramatic survival advantage in glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, modulating malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Glioblastoma

SUBMITTER: Danielle Swaney

LAB HEAD: Nevan Krogan

PROVIDER: PXD034586 | Pride | 2024-11-26

REPOSITORIES: Pride

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			Action	DRS
	EGFRvIII_WWeiss.fasta	Fasta
	MaxQuant_v1.5.5.1.zip	Other
	Sample_Annotations.xlsx	Xlsx
	SearchResults.zip	Other
	checksum.txt	Txt

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Publications

EGFR and EGFRvIII coopt host defense pathways, promoting progression in glioblastoma.

An Zhenyi Z Fan Qi-Wen QW Wang Linyu L Yoda Hiroyuki H Barata Megumi J MJ Jimenez-Morales David D Phillips Joanna J JJ Swaney Danielle L DL Stevenson Erica E Lee Ethan E Krogan Nevan N Weiss William A WA

Neuro-oncology 20240909

<h4>Background</h4>Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma.<h4>Methods</h4>We used phospho-proteomics, RNA-sequencing, TCGA data and glioblastoma cell culture and mouse models to study the signal transduction mediated by EGFR and EGFRvIII.<h4>Results</h4>We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockout of TLR2 dramatically impro ...[more]

PMID: 39248287

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