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Transcriptional Activation Of Integrin Beta6 During The Epithelial-mesenchymal Transition Defines A Novel Prognostic Indicator Of Aggressive Colon Carcinoma.

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Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic

Richard C Bates1, David I Bellovin, Courtney Brown

  • 1Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. rbates@caregroup.harvard.edu

The Journal of Clinical Investigation
|January 26, 2005

View abstract on PubMed

Summary
This summary is machine-generated.

The epithelial-mesenchymal transition (EMT) increases alphavbeta6 integrin expression in colon cancer, promoting tumor growth and migration. High beta6 integrin levels independently predict reduced survival in colorectal cancer patients, especially in early stages.

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Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • The epithelial-mesenchymal transition (EMT) is crucial for carcinoma progression, enabling cells to acquire aggressive phenotypes.
  • Understanding integrin dynamics during EMT is key to deciphering cancer aggressiveness.

Purpose of the Study:

  • To analyze integrin dynamics during EMT in a colon carcinoma spheroid model.
  • To investigate the clinical relevance of beta6 integrin expression in colorectal cancer patients.

Main Methods:

  • Utilized a colon carcinoma spheroid model to study EMT and integrin expression.
  • Performed Kaplan-Meier, log-rank, and Cox regression analyses on patient data (n=488) correlating beta6 expression with survival.

Main Results:

  • EMT induces beta6 integrin subunit expression, leading to increased alphavbeta6 integrin.
  • Alphavbeta6 integrin enhances colon carcinoma tumorigenic properties, including TGF-beta activation and migration.
  • High beta6 integrin expression significantly reduces median survival in colorectal cancer patients, independent of tumor stage.

Conclusions:

  • Alphavbeta6 integrin is a critical mediator of EMT-driven colon carcinoma progression.
  • Elevated alphavbeta6 integrin is an independent prognostic factor and risk factor for early-stage colorectal cancer.
  • Alphavbeta6 integrin represents a potential therapeutic target for colorectal cancer.