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Updated: Jun 9, 2026
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
Summary
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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