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ARID2 Deficiency Enhances Tumor Progression via ERBB3 Signaling in TFE3-Rearranged Renal Cell Carcinoma

Jinglong Tang1, Shintaro Funasaki2, Hidekazu Nishizawa1

  • 1Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Current Issues in Molecular Biology
|December 27, 2024
PubMed

Insights

ARID2 acts as a tumor suppressor in TFE3-rearranged Renal Cell Carcinoma (TFE3-RCC). Loss of ARID2 promotes TFE3-RCC growth and ERBB3 signaling, suggesting ERBB3 inhibition as a potential therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • TFE3-rearranged Renal Cell Carcinoma (TFE3-RCC) is an aggressive cancer with limited therapeutic options.
  • The SWI/SNF complex component ARID2's role in TFE3-RCC is not well understood.

Purpose of the Study:

  • To investigate the function of ARID2 in TFE3-RCC.
  • To explore the therapeutic potential of targeting ERBB3 in ARID2-deficient TFE3-RCC.

Main Methods:

  • In vitro and in vivo experiments including ARID2 knockout (KO) models.
  • Transcriptomic analysis and Chromatin Immunoprecipitation (ChIP) assays.
  • Assessment of cell migration, proliferation, and signaling pathway activation.

Main Results:

  • ARID2 functions as a tumor suppressor in TFE3-RCC, with ARID2 KO enhancing tumor growth and migration.
  • PRCC-TFE3 directly upregulates ERBB3 expression, an effect amplified by ARID2 loss.
  • ARID2-deficient TFE3-RCC cells show increased ERBB3/EGFR/MAPK pathway activation and sensitivity to ERBB3 inhibition.

Conclusions:

  • The PRCC-TFE3-ARID2-ERBB3 axis is crucial in TFE3-RCC pathogenesis.
  • Targeting ERBB3 presents a promising therapeutic strategy for ARID2-deficient TFE3-RCC.
Keywords:
ARID2ERBB3TFE3 fusionTFE3-RCC

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