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Updated: Nov 21, 2025

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Published on: April 22, 2019

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Effects of decreased Rac activity and malignant state on oral squamous cell carcinoma in vitro

Yudai Matsuoka1, Hani Al-Shareef2, Mikihiko Kogo1

  • 1The First Department of Oral & Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.

Plos One
|January 14, 2021
PubMed

Insights

Inhibiting Rac proteins triggered apoptosis in aggressive oral cancer cells by activating JNK. The effectiveness of Rac inhibition for cancer therapy depends on the cancer

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Rac proteins, Rho family GTPases, regulate critical cellular processes like cytoskeleton organization, proliferation, migration, and cancer cell motility.
  • Aberrant Rac protein activity, through gene overexpression, protein up-regulation, or mutation, is common in human cancers and affects cell survival and apoptosis.

Purpose of the Study:

  • To investigate the effects of Rac inhibition on oral squamous cell carcinoma (OSCC) cell lines with varying malignancy grades.
  • To determine the correlation between Rac activity, JNK activation, and apoptosis induction in OSCC.

Main Methods:

  • Utilized a Rac-specific inhibitor (NSC23766) and dominant-negative Rac (Rac-DN) to suppress Rac activity in OSCC cell lines (OSC-20, OSC-19, HOC313) and fibroblasts.
  • Assessed changes in Rac activity, nuclear morphology, JNK activation, and caspase-dependent apoptosis.

Main Results:

  • Inhibition of Rac significantly reduced Rac activity in highly malignant OSC-19 and HOC313 cells, leading to nuclear condensation, JNK activation, and apoptosis.
  • Less malignant OSC-20 cells and normal fibroblasts showed only minor decreases in Rac activity with no significant JNK activation or nuclear changes.
  • Apoptosis induction by Rac inhibition was dependent on the degree of Rac activity reduction and the cancer cell's malignancy grade.

Conclusions:

  • Rac inhibition's ability to induce apoptosis is linked to the extent of Rac activity suppression and the malignancy of the squamous cell carcinoma.
  • JNK activation strongly correlates with Rac inhibition-induced apoptosis, suggesting a key role in the apoptotic pathway.
  • Targeting Rac proteins presents a potential novel therapeutic strategy for treating oral squamous cell carcinoma.

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