GRB10
Overview
GRB10 encodes growth factor receptor-bound protein 10, an adaptor protein that negatively regulates PI3K/insulin signaling by binding to and inhibiting receptor tyrosine kinases including the insulin receptor and IGF1R. In ccRCC, GRB10 promoter methylation is prognostic and represents an epigenetic mechanism of tumor suppressor silencing in the PI3K/AKT/mTOR pathway.
Alterations observed in the corpus
- Promoter methylation pattern is prognostic in clear-cell renal cell carcinoma (ccRCC); functions as a tumor suppressor that negatively regulates PI3K/insulin signaling; miR-21/GRB10 methylation axis proposed as both a prognostic marker and a candidate therapeutic-vulnerability indicator given the Warburg-like metabolic shift in aggressive tumors PMID:23792563
Cancer types (linked)
- CCRCC — epigenetic silencing via promoter methylation; GRB10 methylation is one of the metabolic biomarkers proposed as prognostic in the TCGA ccRCC cohort PMID:23792563
Co-occurrence and mutual exclusivity
- Part of the PI3K/AKT/mTOR pathway alteration landscape in ccRCC; GRB10 loss reinforces PI3K pathway activation alongside mutations in PTEN, MTOR, and amplification of the 5q35.3 amplicon (RACK1, SQSTM1) PMID:23792563
Therapeutic relevance
- PI3K/AKT/mTOR pathway is explicitly nominated as a therapeutic target in ccRCC; GRB10 methylation-driven pathway activation supports the rationale for mTOR inhibitors (everolimus, temsirolimus) in advanced disease PMID:23792563
Open questions
- The specific frequency of GRB10 promoter methylation in the TCGA ccRCC cohort and its independent prognostic contribution relative to other PI3K pathway alterations are not individually detailed PMID:23792563
Sources
This page was processed by crosslinker on 2026-05-09.