Endolysosomal TRPMLs in Cancer

Abstract

Lysosomes, the degradative endpoints and sophisticated cellular signaling hubs, are emerging as intracellular Ca2+ stores that govern multiple cellular processes. Dys-homeostasis of lysosomal Ca2+ is intimately associated with a variety of human diseases including cancer. Recent studies have suggested that the Ca2+-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.

Magneto-mechanical destruction of cancer-associated fibroblasts using ultra-small iron oxide nanoparticles and low frequency rotating magnetic fields

“…27-28, 33, 39, 54 Several ion channels, transient receptor potential ion channels TRPML and two-pores channels TPC, have been identified in endo-lysosomal compartment whose overexpression in cancers increases cell proliferation, migration, invasion and/or metastasis. [55][56][57] These channels are osmo-mechanical sensitive as they can be activated by both physical and chemical signals (oxidants, pH, and osmo-mechanical force). Noticeably, the magnetic forces of USPION@Gastrin assembly calculated by our simulations -few pN -, are large enough to activate such ion channels.…”

Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients

“…Mutations in TRPPs cause autosomal dominant polycystic kidney disease and are also involved in taste perception and fertilization processes ( Su et al, 2018 ). TRPML1-3 mediate endo-lysosomal functions such as autophagy, pH regulation and lysosomal exocytosis that are closely related to cancer development ( Jaślan et al, 2020 ; Xu and Dong, 2021 ). TRPN contributes to the adaption of mechanosensory transduction currents such as tactile sense, auditory, and proprioception, independent of their ion-conduction function ( Jin et al, 2017 ; Li et al, 2021 ).…”

The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment

“…The ion channels belonging to the TRP family are heterogeneously expressed in different cancer types [ 26 , 27 ]. Although TRP channels have been described in different hematological malignancy, information in MM is limited.…”