Regulation of tumor growth via intracellular membrane compartments

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Tumor growth is promoted by persistent activation of growth signaling, which is caused by mutations of various proto-oncogenes. In this study, we investigated the function and regulation mechanisms of the major growth signaling pathways, the MAPK and mTOR pathways, via the scaffold protein p18 that is anchored to the surface of lysosomes. Using p18 knockout cells and mice, we found that p18 forms a regulatory complex (Ragulator) required for activation of mTORC1, and plays crucial roles in regulating cell growth, proliferation, differentiation, and tumor growth. We also clarified the roles of the p18-mTORC1 pathway in the regulation of cell cycle via the transcription factor FoxO3a and lysosome-mediated catabolism. These finding shed new lights on the roles of the intracellular membrane compartments, e.g. lysosomes, in the regulation of tumor promoting signaling.