{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:05:08Z","timestamp":1781244308748,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T00:00:00Z","timestamp":1394150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2014,5]]},"abstract":"Abstract<\/jats:title>Tuberous sclerosis complex (TSC<\/jats:styled-content>) is caused by mutations in TSC<\/jats:styled-content>1<\/jats:italic> or TSC<\/jats:styled-content>2<\/jats:italic> genes. Lymphangioleiomyomatosis (LAM<\/jats:styled-content>) can be sporadic or associated with TSC<\/jats:styled-content> and is characterized by widespread pulmonary proliferation of abnormal \u03b1\u2010smooth muscle (ASM<\/jats:styled-content>)\u2010like cells. We investigated the features of ASM<\/jats:styled-content> cells isolated from chylous thorax of a patient affected by LAM<\/jats:styled-content> associated with TSC<\/jats:styled-content>, named LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cells, bearing a germline TSC<\/jats:styled-content>2<\/jats:italic> mutation and an epigenetic defect causing the absence of tuberin. Proliferation of LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cells is epidermal growth factor (EGF<\/jats:styled-content>)\u2010dependent and blockade of EGF<\/jats:styled-content> receptor causes cell death as we previously showed in cells lacking tuberin. LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cells spontaneously detach probably for the inactivation of the focal adhesion kinase (FAK)\/Akt\/mTOR<\/jats:styled-content> pathway and display the ability to survive independently from adhesion. Non\u2010adherent LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cells show an extremely low proliferation rate consistent with tumour stem\u2010cell characteristics. Moreover, LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cells bear characteristics of stemness and secrete high amount of interleukin (IL<\/jats:styled-content>)\u20106 and IL<\/jats:styled-content>\u20108. Anti\u2010EGF<\/jats:styled-content> receptor antibodies and rapamycin affect proliferation and viability of non\u2010adherent cells. In conclusion, the understanding of LAM<\/jats:styled-content>\/TSC<\/jats:styled-content> cell features is important in the assessment of cell invasiveness in LAM<\/jats:styled-content> and TSC<\/jats:styled-content> and should provide a useful model to test therapeutic approaches aimed at controlling their migratory ability.<\/jats:p>","DOI":"10.1111\/jcmm.12237","type":"journal-article","created":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T12:06:41Z","timestamp":1394194001000},"page":"766-779","source":"Crossref","is-referenced-by-count":19,"title":["TSC<\/scp>2<\/i> epigenetic defect in primary LAM<\/scp> cells. 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