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Updated: Apr 29, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid

Li Jiang1, Yoriko Yamashita, Shan-Hwu Chew

  • 1Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Japan.

The Journal of Pathology
|May 21, 2014
PubMed

Insights

Connective tissue growth factor (Ctgf) drives aggressive sarcomatoid malignant mesothelioma (MM) by promoting proliferation and invasion. Ctgf is a potential biomarker and therapeutic target for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Malignant mesothelioma (MM) is a serious cancer linked to asbestos exposure.
  • Sarcomatoid MM (SM) is the most aggressive subtype with a poor prognosis.
  • Understanding the molecular drivers of SM is crucial for developing new treatments.

Purpose of the Study:

  • To identify genes contributing to the aggressiveness of sarcomatoid malignant mesothelioma (SM).
  • To investigate the role of connective tissue growth factor (Ctgf) in SM progression.
  • To explore Ctgf as a potential diagnostic and prognostic biomarker for MM.

Main Methods:

  • Induction of epithelioid (EM) and sarcomatoid (SM) MM in rats using asbestos.
  • Comparative transcriptome analysis between EM and SM subtypes.
  • Investigation of the Ctgf signaling pathway, including the β-catenin-TCF-LEF pathway and LRP6 receptor.

Main Results:

  • Ctgf expression was significantly elevated in SM compared to EM and normal mesothelium.
  • Ctgf drives SM proliferation and invasion via an autocrine β-catenin-TCF-LEF signaling loop.
  • High Ctgf expression correlated with epithelial-mesenchymal transition and serves as a serum biomarker in rats.

Conclusions:

  • Ctgf is a key regulator of aggressive sarcomatoid malignant mesothelioma.
  • The Ctgf-LRP6-GSK3β-β-catenin-TCF-Ctgf axis drives SM progression.
  • Ctgf represents a promising therapeutic target and diagnostic/prognostic biomarker for MM.
Keywords:
connective tissue growth factormesotheliomasarcomatoid mesotheliomaserum markerβ-catenin

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