Relevance of lysosomal Ca2+ signalling machinery in cancer. (March 2022)

• Record Type: Journal Article
• Authors: Barbonari, Samantha; D'Amore, Antonella; Palombi, Fioretta; De Cesaris, Paola; Parrington, John; Riccioli, Anna; Filippini, Antonio
• Is Part Of: Cell calcium. Volume 102(2022)
• Publication Date: 2022-03
• Subjects: VOCCs voltage-operated calcium channels -- TPCs Two-Pore Channels -- TRPMLs Transient Receptor Potential Cation Channels -- P2X4R Purinergic X Receptor 4 -- NAADP nicotinic acid adenine dinucleotide phosphate; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2022.102539
• Languages: English
• ISSNs: 0143-4160

Abstract

Highlights: Cancer cells contain high amount of lysosomes. Dysfunctional Ca 2+ signalling in cancer is currently a cutting-edge research topic. Endolysosomal Ca 2+ signalling regulates immune cell repertoire in the tumour microenvironment. Lysosomal Ca 2+ channels play an emerging role in autophagy, tumour neoangiogenesis and cancer progression. Lysosomal Ca 2+ channels may represent novel druggable targets in cancer therapy. Abstract: In comparison with normal cells, cancer cells are equipped with a higher number of lysosomes, involved in degradative and non-degradative roles. In particular, the lysosome is a Ca 2+ signalling hub, and the enhancement of this interconnected machinery in cancer cells has recently prompted investigations into the role that lysosomal ion channels play in oncology. The present review reports findings about the emerging role of lysosomal Ca 2+ channels: Two-Pore Channels (TPCs), Transient Receptor Potential Cation Channels (TRPMLs; mucolipins), and Purinergic X Receptor 4 (P2×4R), in a variety of cancer models, highlighting their impact on crucial functions such as the regulation of autophagy and the composition of the tumour microenvironment, including the secretion-mediated interplay with immune and endothelial cells. Notably, recent evidence indicates that, by regulating tumour secretome, lysosomal Ca 2+ signalling can affect the composition of the tumour-infiltrating immune cell repertoire. Intriguingly, the data so far available show that the protumoral/antitumoral role of lysosomal Ca 2+ channels can differ according to the specific genetic context, types of cancer and the malignancy stage, and signals from the microenvironment. Graphical abstract: Image, graphical abstract