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RhoC GTPase Activation Assay
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Loss of RhoA promotes skin tumor formation and invasion by upregulation of RhoB

A García-Mariscal1, H Li1, E Pedersen1

  • 1Biotech Research and Innovation Centre, BRIC, University of Copenhagen, Copenhagen, Denmark.

Oncogene
|October 24, 2017
PubMed

Insights

Loss of RhoA, a protein controlling cell movement, surprisingly accelerates skin tumor formation and invasion. This occurs due to RhoB overcompensation, highlighting Rho signaling

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Cellular movement is regulated by small GTPases, including RhoA.
  • The role of RhoA in tumor formation and cancer cell invasion is not fully understood.

Purpose of the Study:

  • To investigate the specific role of RhoA in skin tumor formation and invasion.
  • To elucidate the underlying molecular mechanisms driving tumor progression in the absence of RhoA.

Main Methods:

  • Induction of skin tumors in mice with keratinocyte-restricted loss of RhoA.
  • In vitro invasion assays.
  • Analysis of RhoB signaling, lysosomal degradation, and protein localization.

Main Results:

  • Loss of RhoA increased tumor frequency, growth, and invasion in mice.
  • Cell invasiveness was enhanced in RhoA-deficient cells via Rho-associated protein kinase (ROCK) activation and cell contraction.
  • RhoA loss led to RhoB overcompensation, with RhoB functionally replacing RhoA in promoting invasion, growth, and survival.

Conclusions:

  • RhoA acts as a tumor suppressor in skin carcinogenesis.
  • Rho signaling, involving both RhoA and RhoB, is a critical driver of tumor progression.

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