Endolysosomal TRPMLs in Cancer

Lysosomes, the degradative endpoints and sophisticated cellular signaling hubs, are emerging as intracellular Ca(2+) stores that govern multiple cellular processes. Dys-homeostasis of lysosomal Ca(2+) is intimately associated with a variety of human diseases including cancer. Recent studies have suggested that the Ca(2+)-permeable channels Transient Receptor Potential (TRP) Mucolipins (TRPMLs, TRPML1-3) integrate multiple processes of cell growth, division and metabolism. Dysregulation of TRPMLs activity has been implicated in cancer development. In this review, we provide a summary of the latest development of TRPMLs in cancer. The expression of TRPMLs in cancer, TRPMLs in cancer cell nutrient sensing, TRPMLs-mediated lysosomal exocytosis in cancer development, TRPMLs in TFEB-mediated gene transcription of cancer cells, TRPMLs in bacteria-related cancer development and TRPMLs-regulated antitumor immunity are discussed. We hope to guide readers toward a more in-depth discussion of the importance of lysosomal TRPMLs in cancer progression and other human diseases.