The Loss of Tuberin Promotes Cell Invasion Through the ß-catenin Pathway

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2010 Jan 1

PMID 20042714

Citations 13

Authors

Elizabeth A Barnes

Heidi L Kenerson

Baldwin C Mak

Raymond S Yeung

Affiliations

Soon will be listed here.

Abstract

Mutations in the tumor suppressor tuberin (TSC2) are a common factor in the development of lymphangioleiomyomatosis (LAM). LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma. The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated, although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells. Here we show that tuberin-null cells become nonadherent and invasive. These nonadherent cells express cleaved forms of β-catenin. In reporter assays, the β-catenin products are transcriptionally active and promote MMP7 expression. Invasion by the tuberin-null cells is mediated by MMP7. Examination of LAM tissues shows the expression of cleaved β-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a β-catenin-dependent mechanism, which may underlie the development of LAM.

Citing Articles

Differential Modulation of Matrix Metalloproteinases-2 and -7 in LAM/TSC Cells.

Ancona S, Orpianesi E, Bernardelli C, Chiaramonte E, Chiaramonte R, Terraneo S Biomedicines. 2021; 9(12).

PMID: 34944575 PMC: 8698908. DOI: 10.3390/biomedicines9121760.

Exploring the Role of Matrix Metalloproteinases as Biomarkers in Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. A Pilot Study.

Terraneo S, Lesma E, Ancona S, Imeri G, Palumbo G, Torre O Front Med (Lausanne). 2021; 8:605909.

PMID: 33981713 PMC: 8107231. DOI: 10.3389/fmed.2021.605909.

CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis.

Evans J, Obraztsova K, Lin S, Krymskaya V Int J Mol Sci. 2021; 22(5).

PMID: 33668092 PMC: 7956553. DOI: 10.3390/ijms22052233.

mTOR and S6K1 drive polycystic kidney by the control of Afadin-dependent oriented cell division.

Bonucci M, Kuperwasser N, Barbe S, Koka V, de Villeneuve D, Zhang C Nat Commun. 2020; 11(1):3200.

PMID: 32581239 PMC: 7314806. DOI: 10.1038/s41467-020-16978-z.

Lymphangioleiomyomatosis: a case report and review of diagnosis and treatment.

Liu Y, Guo Z, Zhao C, Li X, Liu H, Chen J Onco Targets Ther. 2018; 11:5339-5347.

PMID: 30214240 PMC: 6126514. DOI: 10.2147/OTT.S161360.

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