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Updated: Dec 14, 2025

RhoC GTPase Activation Assay
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Leukemia-Associated Rho Guanine Nucleotide Exchange Factor and Ras Homolog Family Member C Play a Role in

Zonghui Ding1, Zhiwan Dong2, Yuping Yang2

  • 1Department of Cancer Biology, Mayo Clinic Arizona, Scottsdale, Arizona.

The American Journal of Pathology
|July 22, 2020
PubMed

Insights

Leukemia-associated Rho guanine nucleotide exchange factor (LARG) and RhoC promote glioblastoma invasion. Inhibiting LARG may also enhance temozolomide treatment effectiveness for brain tumors.

Area of Science:

  • Neuro-oncology
  • Cancer biology
  • Molecular mechanisms of cancer progression

Background:

  • Glioblastoma (GBM) is an aggressive brain cancer characterized by invasive tumor cells.
  • Current therapies are insufficient to halt GBM invasion.
  • Leukemia-associated Rho guanine nucleotide exchange factor (LARG) is implicated in other cancers but its role in GBM is unknown.

Purpose of the Study:

  • To investigate the role of LARG and its downstream effectors, RhoC and RhoA, in GBM cell migration and invasion.
  • To explore LARG as a potential therapeutic target for inhibiting glioma invasion and enhancing chemotherapy response.

Main Methods:

  • Quantitative analysis of LARG, RhoA, and RhoC protein expression in glial tumors of varying grades.
  • In vitro and ex vivo assays using siRNA to knockdown LARG, RhoC, and RhoA in GBM cells.
  • Assessment of GBM cell migration and invasion following gene silencing.
  • Evaluation of temozolomide sensitivity in GBM cells with LARG depletion.

Main Results:

  • LARG, RhoC, and RhoA expression increases with glial tumor grade, peaking in GBM.
  • LARG and RhoC are predominantly expressed in invading GBM cells.
  • LARG and RhoC knockdown inhibits GBM cell migration and invasion.
  • RhoA depletion enhances GBM cell migration and invasion.
  • LARG depletion sensitizes GBM cells to temozolomide.

Conclusions:

  • LARG and RhoC are key regulators of GBM cell invasion.
  • Targeting LARG and RhoC may offer a novel strategy to inhibit glioma spread.
  • LARG inhibition could potentiate the efficacy of standard chemotherapy for glioblastoma.

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