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Updated: Aug 10, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis

K Matsuzaki1

  • 1Department of Gastroenterology and Hepatology, Kansai Medical University, Moriguchi, Osaka, Japan. matsuzak@takii.kmu.ac.jp

Histology and Histopathology
|March 11, 2006
PubMed

Insights

Transforming growth factor-beta (TGF-beta) signaling shifts during colorectal cancer, with JNK/pSmad3L promoting invasion and TbetaRI/pSmad3C inhibiting growth. This pathway switch drives cancer progression and metastasis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • Transforming growth factor-beta (TGF-beta) signaling plays a dual role in human colorectal carcinogenesis.
  • TGF-beta normally inhibits epithelial cell proliferation but promotes invasion and metastasis in later stages.

Purpose of the Study:

  • To elucidate the shift in TGF-beta signaling during colorectal cancer progression.
  • To understand the roles of Smad3 phosphoisoforms (pSmad3C and pSmad3L) in mediating these opposing functions.
  • To explore the cross-talk between TGF-beta and c-Jun N-terminal kinase (JNK) pathways.

Main Methods:

  • Review of existing literature on TGF-beta signaling, Smad3 phosphorylation, and JNK pathway activation in colorectal cancer.
  • Analysis of Smad3 phosphoisoform dynamics (pSmad3C vs. pSmad3L) during neoplastic progression.
  • Investigation of signaling cross-talk between TGF-beta, JNK, and hepatocyte growth factor.

Main Results:

  • TGF-beta signaling shifts from antiproliferative TbetaRI/pSmad3C to pro-invasive JNK/pSmad3L pathways.
  • JNK activation by TGF-beta generates pSmad3L, promoting tumor cell invasion and extracellular matrix synthesis.
  • Increased nuclear pSmad3L and decreased pSmad3C correlate with colorectal cancer progression from adenoma to invasive adenocarcinoma.

Conclusions:

  • The shift from TbetaRI/pSmad3C to JNK/pSmad3L signaling is a key mechanism in colorectal carcinogenesis.
  • Cross-talk between Smad3 and JNK pathways drives oncogenic activities and metastasis.
  • Targeting the JNK/pSmad3L pathway offers a potential therapeutic strategy for colorectal cancer.

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