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Updated: Jun 9, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal transition

Elizabeth A Barnes1, Heidi L Kenerson, Xiuyun Jiang

  • 1Department of Surgery, University of Washington, Seattle, Washington 98195, USA.

The American Journal of Pathology
|September 4, 2010
PubMed

Insights

Loss of the TSC2 gene causes abnormal cell growth in tuberous sclerosis and lymphangioleiomyomatosis. This study reveals TSC2 regulates E-cadherin, impacting cell adhesion and promoting epithelial-mesenchymal transition (EMT) in these diseases.

Area of Science:

  • Cell Biology
  • Genetics
  • Oncology

Background:

  • Tuberous sclerosis complex 2 (TSC2) encodes tuberin, a negative regulator of mammalian target of rapamycin (mTOR) C1 signaling.
  • Loss-of-function mutations in TSC2 lead to mTORC1 hyperactivity, causing tuberous sclerosis and lymphangioleiomyomatosis, characterized by smooth muscle-like cell proliferation.
  • The metastatic potential and the role of the mTOR pathway in these diseases are not fully understood.

Purpose of the Study:

  • To investigate the role of tuberin in regulating cell adhesion and epithelial-mesenchymal transition (EMT).
  • To elucidate the mechanism by which the TSC2/mTORC1 pathway influences E-cadherin localization and cell behavior.

Main Methods:

  • Utilized Tsc2(-/-) epithelial cells to study E-cadherin regulation and EMT.
  • Analyzed cell-cell adhesion, plasma membrane E-cadherin levels, and expression of EMT markers (E-cadherin, occludin, Snail, smooth muscle actin).
  • Assessed functional changes including anchorage-independent growth, cell scattering, and anoikis resistance. Examined human disease tissues for EMT markers.

Main Results:

  • Tuberin regulates E-cadherin localization through an Akt/mTORC1/CLIP170 pathway.
  • Tsc2(-/-) cells exhibit reduced E-cadherin at the plasma membrane, leading to decreased cell adhesion.
  • These cells undergo EMT, characterized by altered expression of adhesion molecules and EMT markers, and display anchorage-independent growth, scattering, and anoikis resistance.
  • Human angiomyolipomas and lymphangioleiomyomatosis tissues show EMT markers and invasive phenotypes.

Conclusions:

  • TSC2/mTORC1 signaling is intricately linked with E-cadherin regulation.
  • EMT is implicated as a key mechanism in the pathogenesis of tuberous sclerosis complex-related diseases.
  • This study provides novel insights into the cellular mechanisms driving these conditions and suggests potential therapeutic targets.

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