Related Experiment Video

Updated: Aug 19, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

RalGDS is required for tumor formation in a model of skin carcinogenesis

Ana González-García1, Catrin A Pritchard, Hugh F Paterson

  • 1Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom.

Cancer Cell
|March 16, 2005
PubMed

Insights

RalGDS is not essential for mouse development but is crucial for Ras-induced cancer. Its absence reduces tumor formation and progression by controlling transformed cell survival via the JNK/SAPK pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The small GTPase Ral is a key regulator in cellular signaling pathways.
  • Guanine nucleotide exchange factors (GEFs) like RalGDS activate small GTPases.
  • The precise role of RalGDS in oncogenesis remains incompletely understood.

Purpose of the Study:

  • To elucidate the function of RalGDS in mammalian development and Ras-driven carcinogenesis.
  • To determine the specific contribution of RalGDS to tumor initiation, growth, and malignant progression.

Main Methods:

  • Generation of RalGDS-deficient mice.
  • Multistage skin carcinogenesis assays in vivo.
  • Ras-mediated cell transformation assays in tissue culture.
  • Analysis of cell proliferation and survival in tumor-derived cells.

Main Results:

  • RalGDS deficiency did not impair normal mouse development.
  • Absence of RalGDS significantly reduced tumor incidence, size, and malignancy in skin carcinogenesis models.
  • RalGDS was dispensable for Ras-induced cell proliferation but critical for transformed cell survival.
  • RalGDS mediates cell survival through the activation of the JNK/SAPK pathway in tumor cells.

Conclusions:

  • RalGDS is a dispensable factor for mouse development.
  • RalGDS plays a critical role in Ras-dependent oncogenesis by promoting transformed cell survival.
  • The JNK/SAPK pathway is a key downstream mediator of RalGDS's pro-survival function in cancer.

More Related Videos

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector05:06

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector

Published on: February 2, 2021

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...