Lysosomal Calcium Channels in Autophagy and Cancer

SIMPLE SUMMARY: Autophagy is a cellular self-eating process that uses lysosome, the waste disposal system of the cell, to degrade and recycle intracellular materials to maintain cellular homeostasis. Defects in autophagy are linked to a variety of pathological states, including cancer. Calcium is an important cellular messenger that regulates the survival of all animal cells. Alterations to calcium homoeostasis are associated with cancer. While it has long been considered as cellular recycling center, the lysosome is now widely known as an intracellular calcium store that regulates autophagy and cancer progression by releasing calcium via some ion channels residing in the lysosomal membrane. In this review, we summarize existing mechanisms of autophagy regulation by lysosomal calcium channels and their implications in cancer development. We hope to guide readers toward a more in-depth understanding of the importance of lysosomal calcium channels in cancer, and potentially facilitate the development of new therapeutics for some cancers. ABSTRACT: Ca(2+) is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca(2+) signaling is regulated by both extracellular Ca(2+) entry and Ca(2+) release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca(2+) store that provides Ca(2+) to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca(2+). In lysosomal Ca(2+)-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca(2+) stores and their roles in autophagy and human cancer progression.