Regulation of LAM cells by a CCL2/MCP-1 positive-feedback loop. TSC2 is a negative regulator of mTOR through conversion of Rheb-GTP to Rheb-GDP. Akt negatively regulates tuberin, which is also a substrate for the LKB1 substrate AMP-dependent kinase. Mutations that lead to dysfunctional TSC2 cause hyperactivation of mTOR. Lack of TSC2 function results in up-regulation of CCL2 production. In addition, CCL2 enhances LAM cell motility and is produced by LAM cells, by other cell types within the lung, or by extra-pulmonary cells, resulting in a positive-feedback loop regulating LAM cell motility.