Elodie Terrié, Valérie Coronas, Bruno Constantin

Cell Calcium 80 (2019) 141–151

A B S T R A C T
Cancer stem cells are a subpopulation of tumor cells that proliferate, self-renew and produce more differentiated
tumoral cells building-up the tumor. Responsible for the sustained growth of malignant tumors, cancer stem cells
are proposed to play significant roles in cancer resistance to standard treatment and in tumor recurrence. Among
the mechanisms dysregulated in neoplasms, those related to Ca2+ play significant roles in various aspects of
cancers. Ca2+ is a ubiquitous second messenger whose fluctuations of its intracellular concentrations are tightly
controlled by channels, pumps, exchangers and Ca2+ binding proteins. These components support the genesis of
Ca2+ signals with specific spatio-temporal characteristics that define the cell response. Being involved in the
coupling of extracellular events with intracellular responses, the Ca2+ toolkit is often hijacked by cancer cells to
promote notably their proliferation and invasion. Growing evidence obtained during the last decade pointed to a
role of Ca2+ handling and mishandling in cancer stem cells. In this review, after a general overview of the
concept of cancer stem cells we analyse and discuss the studies and current knowledge regarding the complex
roles of Ca2+ toolkit and signaling in these cells. We highlight that numbers of Ca2+ signaling actors promote
cancer stem cell state and are associated with cell resistance to current cancer treatments and thus may represent
promising targets for potential clinical applications.