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Updated: May 7, 2025

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

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Upregulation of GSTP1 mediated by chimeric TFE3 promotes TFE3-tRCC progression by targeting JNK signaling pathway

Weixu Chen1, Mengtong Wu1, Lin Du2

  • 1Department of Urology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, 210008, China.

World Journal of Surgical Oncology
|December 30, 2024
PubMed
Abstract

Insights

Glutathione S-transferase pi 1 (GSTP1) upregulation drives TFE3-translocation renal cell carcinoma (TFE3-tRCC) progression. Targeting GSTP1 offers a promising therapeutic strategy for this kidney cancer subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a kidney cancer subtype lacking effective treatments and biomarkers.
  • Xp11.2 translocations involving TFE3 fusions are characteristic of TFE3-tRCC.

Purpose of the Study:

  • To elucidate pathogenic mechanisms in TFE3-tRCC.
  • To identify novel therapeutic targets for advanced TFE3-tRCC.

Main Methods:

  • RNA sequencing of 14 untreated TFE3-tRCC patients.
  • qRT-PCR and Western blot for gene and protein expression analysis.
  • Cell proliferation, apoptosis, migration, and invasion assays were performed.

Main Results:

  • GSTP1 expression was upregulated in TFE3-tRCC.
  • ASPL-TFE3 fusion protein localized to the nucleus, promoting tumorigenesis.
  • GSTP1 inhibition via siRNA or Ezatiostat reduced tumor growth and induced apoptosis.
  • GSTP1 drives TFE3-tRCC progression by modulating the JNK signaling pathway.

Conclusions:

  • Chimeric TFE3 upregulates GSTP1, promoting TFE3-tRCC progression via the JNK pathway.
  • GSTP1 represents a potential therapeutic target for TFE3-tRCC.
Keywords:
ASPL-TFE3EzatiostatGSTP1JNK signaling pathwayTFE3-tRCC

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