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Updated: Jun 3, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

RASD2 Drives Renal Clear Cell Carcinoma Progression via RAF1 (Ser338) Phosphorylation

Jingxuan Yu1,2, Gang Yu3, Yuan Liu4

  • 1Department of Urology, Postgraduate Union Training Base of General Hospital of Central Theater Command, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.

Cancer Science
|June 2, 2026
PubMed

Insights

RASD2 is overexpressed in kidney cancer, promoting tumor growth and spread by activating the P38/ERK-MAPK pathway via RAF1. Inhibiting RAF1 shows promise for treating clear cell renal cell carcinoma (ccRCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer with few treatments.
  • The role of RASD2 in ccRCC tumorigenesis is currently unknown.
  • RASD2, a Ras-related GTP-binding protein, is implicated in melanoma progression.

Purpose of the Study:

  • To investigate the oncogenic functions and molecular mechanisms of RASD2 in ccRCC.
  • To determine if RASD2 plays a role in ccRCC progression and patient prognosis.
  • To explore potential therapeutic strategies targeting RASD2-mediated pathways.

Main Methods:

  • Analysis of RASD2 expression in ccRCC tissues and correlation with patient prognosis.
  • In vitro functional assays (proliferation, migration, invasion) and in vivo xenograft models.
  • Mechanistic studies involving pathway activation (P38/ERK-MAPK), protein interaction (co-immunoprecipitation, LC-MS/MS), and drug inhibition (BAY43-9006).

Main Results:

  • RASD2 is significantly overexpressed in ccRCC tumors and linked to poor prognosis.
  • RASD2 promotes ccRCC cell proliferation, migration, and invasion in vitro and in vivo.
  • RASD2 activates the P38/ERK-MAPK pathway by enhancing RAF1 phosphorylation at Ser338, which is critical for ccRCC growth.
  • RAF1 inhibition suppressed ccRCC progression and tumor growth.

Conclusions:

  • RASD2 acts as an oncoprotein in ccRCC, driving tumorigenesis through RAF1-mediated P38/ERK-MAPK pathway activation.
  • Targeting RAF1 represents a potential therapeutic strategy for ccRCC patients.
  • RASD2 is a novel therapeutic target for clear cell renal cell carcinoma.
Keywords:
P38/ERK–MAPK signalingRAF1RASD2ccRCC

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