Role of the calcium toolkit in cancer stem cells

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.