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Updated: Mar 2, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Published on: October 27, 2020

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A Smad3-PTEN regulatory loop controls proliferation and apoptotic responses to TGF-β in mouse endometrium

Nuria Eritja1,2, Isidre Felip1, Mari Alba Dosil1,2

  • 1Department de Ciències Mèdiques Bàsiques, Oncologic Pathology Group, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain.

Cell Death and Differentiation
|May 20, 2017
PubMed

Insights

The Smad3-PTEN signaling axis dictates cellular responses to TGF-β by regulating apoptosis and proliferation. This axis involves Smad3 activating PTEN, which inhibits the PI3K/AKT pathway, influencing cancer development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-β) signaling pathways, including TGF-β/Smad and PI3K/AKT, are crucial for cell proliferation and apoptosis.
  • Dysregulation of these pathways is implicated in cancer development, with TGF-β exhibiting context-dependent tumor suppressor or promoter roles.

Purpose of the Study:

  • To elucidate the intricate crosstalk between TGF-β/Smad and PI3K/AKT signaling pathways.
  • To investigate the role of a novel PTEN-Smad3 regulatory loop in cellular responses to TGF-β.

Main Methods:

  • Investigated TGF-β-induced apoptosis in wild-type and genetically modified endometrial epithelial cells.
  • Utilized Smad3 knockdown/knockout and PTEN knockout models.
  • Analyzed PTEN transcription, PI3K/AKT signaling pathway activity, and cell proliferation rates.

Main Results:

  • TGF-β induces apoptosis in wild-type endometrial cells via Smad3-dependent PTEN activation, inhibiting PI3K/AKT signaling.
  • Smad3 deficiency or knockout blocks TGF-β-induced apoptosis and promotes proliferation by reducing PTEN expression.
  • PTEN knockout mimics Smad3 deletion, preventing TGF-β-induced apoptosis and enhancing proliferation through increased PI3K/AKT/mTOR signaling.

Conclusions:

  • The Smad3-PTEN signaling axis is a key determinant of cellular responses to TGF-β.
  • This axis plays a critical role in balancing apoptosis and proliferation in endometrial epithelial cells.
  • Understanding this regulatory loop offers new insights into cancer development and potential therapeutic strategies.

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