Role of Sigma-1 Receptor in Calcium Modulation: Possible Involvement in Cancer

Ca²⁺ signaling plays a pivotal role in the control of cellular homeostasis and aberrant regulation of Ca²⁺ fluxes have a strong impact on cellular functioning. As a consequence of this ubiquitous role, Ca²⁺ signaling dysregulation is involved in the pathophysiology of multiple diseases including cancer. Indeed, multiple studies have highlighted the role of Ca²⁺ fluxes in all the steps of cancer progression. In particular, the transfer of Ca²⁺ at the ER-mitochondrial contact sites, also known as mitochondrial associated membranes (MAMs), has been shown to be crucial for cancer cell survival. One of the proteins enriched at this site is the sigma-1 receptor (S1R), a protein that has been described as a Ca²⁺-sensitive chaperone that exerts a protective function in cells in various ways, including the modulation of Ca²⁺ signaling. Interestingly, S1R is overexpressed in many types of cancer even though the exact mechanisms by which it promotes cell survival are not fully elucidated. This review summarizes the findings describing the roles of S1R in the control of Ca²⁺ signaling and its involvement in cancer progression.