The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation is reminiscent of cells undergoing epithelial-mesenchymal transition (EMT). Src kinases are key regulators of cellular proliferation, motility, invasiveness and EMT. Recent results have shown that autophagy promotes degradation of active Src. Thereby, decreased autophagy due to mTOR activation known to occur in LAM cells, may play a significant role in accumulation of active Src in these cells. Src suppresses transcription of E-cadherin by upregulating its transcriptional repressors. The preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in cultured TSC2-/- cells. Further, in TSC2-/- cells, E-cadherin is considerably reduced and does not localize to the plasma membrane, as it does in wild-type cells.