Abstract
The transient receptor potential mucolipin 1 (TRPML1) is an endolysosomal channel belonging to the TRP family. Clinically, mutations of TRPML1 have been responsible for a severe lysosomal storage disorder called mucolipidosis type IV.
The TRPML1 channels localize mainly in the endosome/lysosome compartments, where they control the endocytosis, exocytosis and autophagy processes.
TRPML1 is a reactive oxygen species sensor that orchestrates an autophagy-dependent program, to mitigate oxidative stress. In homeostatic condition TRPML1 controls cell viability; mild stress stimulates macroautophagy or chaperone-mediated autophagy and cell survival, whereas in severe cellular stress conditions it triggers autophagic cell death or apoptosis.
Changes in TRP channels expression are associated with cancer transformation. In the same view, both up and down-regulation of TRPML1 mRNA and protein expression is associated with different cancer types. HRAS-mutated head and neck and bladder urothelial cancers, non-small-cell lung carcinoma, melanomas, triple-negative breast cancers and pancreatic cancer, all show TRPML1 up-regulation. At the other hand, TRPML1 is down-regulated in glioblastoma and reduction/loss of TRPML1 represents a negative prognostic factor.
An increased level of complexity of the TRPML1 channel is represented by its capability to form homo- and heterodimers with other members of TRPML or two-pore channels forming new functional channels. Finally, the TFEB transcriptional factor, targeting the TRPML1 promoter is altered in pancreatic cancer and is associated with poor prognosis of non-small-cell lung carcinoma patients. Overall, we present interesting and recent data strongly suggesting for an important role played by TRPML1 in cancer. Further researches are needed to understand in depth contribution of this channel in the neoplastic transformation and progression of cancer.
Keywords
TRP; TRPML1; Ion channel; Lysosome; Autophagy; Cell death; Cancer