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Updated: Dec 10, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Regulation of epithelial-mesenchymal transition and organoid morphogenesis by a novel TGFβ-TCF7L2 isoform-specific

Kunal Karve1, Stuart Netherton1, Lili Deng1

  • 1Department of Biochemistry and Molecular Biology, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Cell Death & Disease
|August 27, 2020
PubMed

Insights

Alternative splicing of the TCF7L2 gene creates isoforms that differentially regulate epithelial-mesenchymal transition (EMT), impacting organoid development. This study reveals isoform-specific functions of TCF7L2 in controlling EMT and tissue morphogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Background:

  • Alternative splicing generates diverse protein isoforms, but its functional consequences remain unclear.
  • The transcription factor TCF7L2 is known to undergo alternative splicing, yet the biological significance of its isoforms is not well understood.

Purpose of the Study:

  • To investigate the isoform-specific functions of TCF7L2 in epithelial tissue morphogenesis.
  • To elucidate the role of TCF7L2 alternative splicing in regulating epithelial-mesenchymal transition (EMT).

Main Methods:

  • Utilized 3D-epithelial organoid models to study morphogenesis.
  • Investigated the effects of TCF7L2 isoforms on EMT.
  • Analyzed the interplay between TCF7L2, transforming growth factor beta (TGFβ) signaling, and Smad3.

Main Results:

  • TCF7L2 E-isoforms maintain organoid morphogenesis, while M and S isoforms disrupt it by regulating EMT.
  • TCF7L2E2 antagonizes EMT-like effects, whereas TCF7L2M2/S2 promotes them, particularly under TGFβ signaling.
  • TGFβ signaling alters the ratio of TCF7L2E to TCF7L2M/S proteins during EMT.

Conclusions:

  • TCF7L2 exhibits novel isoform-specific functions in controlling EMT and epithelial tissue morphogenesis.
  • Established a link between TCF7L2 and TGFβ-Smad3 signaling in the regulation of EMT.

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