The growth and multiplication of cells in our body are strictly regulated to secure that tissues and organs keep functioning and to prevent cancer. A key regulator in this process is mTORC1, a large protein complex that is present in all cells throughout the body. mTORC1 only stimulates cell growth when the cell detects enough biomaterial needed for growth and an actual growth-allowance signal as well as the absence of stress signals. Cancer cells often work around the strict regulation of mTORC1 to grow and divide independently of proper growth signals. The TSC complex is yet another large protein complex that is the major controller of mTORC1. TSC strongly inhibits mTORC1, but TSC is made inactive when it detects the above-mentioned collective growth-allowing signals. Not surprisingly, in cancer TSC function is often suppressed causing unrestrained activation of mTORC1 and cancer cell growth.
However, in some types of cancer, including the highly malignant small cell lung cancer, the TCS complex is fully functional and able to suppress mTORC1 growth signals. Although counterintuitive, TSC function in these cancer cells is required for cell survival and tumor growth. In this thesis of Josephine Hartung this unique dependence on TSC-mTORC1 regulation may offer opportunities for new anti-cancer treatment by drugs that inhibit TSC function.
Therefore, we aimed to unravel the mechanism behind this atypical behavior of the TSC complex in small cell lung cancer, and we set out to develop a screening system for the identification of potential drugs that kill small cell lung cancer cells.
