ArticleThe American journal of pathology2010
Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal transition.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Current insight into the molecular mechanisms of lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2026Review
- Polyploidy and Senescence of Cancer Cells: Impact of Cell Fusion.Advances in experimental medicine and biology · 2026Review
- Veneer Is a Webtool for Rapid, Standardized, and Transparent Interpretation, Annotation, and Reporting of Mammalian Cell SurfaceJournal of proteome research · 2024Article
- An Overview of Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Canine Tumors: How Far Have We Come?Veterinary sciences · 2022Review
- Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Long-Term Effects of Sirolimus on Human Skin TSC2-Null Fibroblast‒Like Cells.The Journal of investigative dermatology · 2021Article
- A novel role of snail in regulating tuberin/AMPK pathways to promote renal fibrosis in the new mouse model of type II diabetes.FASEB bioAdvances · 2021Article
- mTOR and S6K1 drive polycystic kidney by the control of Afadin-dependent oriented cell division.Nature communications · 2020Article
- Allosteric and ATP-Competitive Inhibitors of mTOR Effectively Suppress Tumor Progression-Associated Epithelial-Mesenchymal Transition in the Kidneys of Tsc2Neoplasia (New York, N.Y.) · 2019Article
- Rapalog resistance is associated with mesenchymal-type changes in Tsc2-null cells.Scientific reports · 2019Article
- Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin.Oncotarget · 2018Article
- Lymphangioleiomyomatosis: a case report and review of diagnosis and treatment.OncoTargets and therapy · 2018Article
- Distinct subcellular localization of E-cadherin between epithelioid angiomyolipoma and triphasic angiomyolipoma: A preliminary case-control study.Oncology letters · 2017Article
- Developmental pathways associated with cancer metastasis: Notch, Wnt, and Hedgehog.Cancer biology & medicine · 2017Article
- Needs and Requirements of Modern Biobanks on the Example of Dystonia Syndromes.Frontiers in neurology · 2017Article
- Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis.JCI insight · 2016Article
- Article
- TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016Review
- EPIDEMIOLOGY, PATHOGENESIS and DIAGNOSIS of LYMPHANGIOLEIOMYOMATOSIS.Expert opinion on orphan drugs · 2016Article
- Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway.Oncology reports · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The tuberous sclerosis complex 2 (TSC2) gene encodes the protein tuberin, which functions as a key negative regulator of both mammalian target of rapamycin (mTOR) C1-dependent cell growth and proliferation. Loss-of-function mutations of TSC2 result in mTORC1 hyperactivity and predispose individuals to both tuberous sclerosis and lymphangioleiomyomatosis. These overlapping diseases have in common the abnormal proliferation of smooth muscle-like cells. Although the origin of these cells is unknown, accumulating evidence suggests that a metastatic mechanism may be involved, but the means by which the mTOR pathway contributes to this disease process remain poorly understood. In this study, we show that tuberin regulates the localization of E-cadherin via an Akt/mTORC1/CLIP170-dependent, rapamycin-sensitive pathway. Consequently, Tsc2(-/-) epithelial cells display a loss of plasma membrane E-cadherin that leads to reduced cell-cell adhesion. Under confluent conditions, these cells detach, grow in suspension, and undergo epithelial-mesenchymal transition (EMT) that is marked by reduced expression levels of both E-cadherin and occludin and increased expression levels of both Snail and smooth muscle actin. Functionally, the Tsc2(-/-) cells demonstrate anchorage-independent growth, cell scattering, and anoikis resistance. Human renal angiomyolipomas and lymphangioleiomyomatosis also express markers of EMT and exhibit an invasive phenotype that can be interpreted as consistent with EMT. Together, these results suggest a novel relationship between TSC2/mTORC1 and the E-cadherin pathways and implicate EMT in the pathogenesis of tuberous sclerosis complex-related diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.