Ca2+ Fluxes and Cancer

Abstract

Ca 2+ ions are key second messengers in both excitable and non-excitable cells. Owing to the rather pleiotropic nature of Ca 2+ transporters and other Ca 2+ -binding proteins, however, Ca 2+ signaling has attracted limited attention as a potential target of anticancer therapy. Here, we discuss cancer-associated alterations of Ca 2+ fluxes at specific organelles as we identify novel candidates for the development of drugs that selectively target Ca 2+ signaling in malignant cells.

Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours

“…Taken together, these findings reveal that alterations in the organization and activity of the MCU complex could represent critical scenarios contributing to the remodelling of the metabolic profile and to the aggressiveness of certain types of cancer (as elegantly reviewed in [58] ).…”

“…In this respect, reduced mitochondrial Ca 2+ uptake is still able to activate the TCA cycle, smoothing the production of reducing equivalents that feed into the ETC and maintaining enough ATP for cellular needs [58] .…”

“…However, many cancer cells benefit from mROS generation through its effects on redox signalling; thus, refined strategies that allow for the specific modulation of mROS must be conceived. Today, several therapeutic approaches are used to modulate mitochondrial Ca 2+ transfer by acting on ER Ca 2+ release [58] . Among these, photodynamic therapy (PDT) and Mipsagargin (G-202) inducing apoptosis by favouring ER Ca 2+ depletion and mitochondrial Ca 2+ overload [ 56 , 112 ].…”

In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes

“…Cellular metabolism appears as a good target to tackle several types of cancer and its regulation by Ca 2+ seems to be a good option to develop new drugs (Bustos et al, 2017). Regarding Ca 2+ , there is accumulated knowledge about the specific role of many ion channels in cancer cell physiology (Marchi et al, 2020). In this context, Xestospongin B (XeB), an alkaloid obtained from the marine sponge Xestospongia exigua, specifically inhibits IP3R-mediated Ca 2+ release (Jaimovich et al, 2005), selectively inducing nonapoptotic cell death of some types of cancer cells (Cárdenas et al, 2017;Cardenas et al, 2020).…”

Roles of NAD+ and Its Metabolites Regulated Calcium Channels in Cancer

“…Moreover, in addition to these regulatory functions, recent work has shown that NAD + and its metabolites also regulate the activity of ion channels, including the Slo K + channels, voltage-gated potassium channels and sodium channels, ATP-regulated K + channels, and some specific types of calcium channels [ 8 ]. Considering the important role of Ca 2+ homeostasis in malignant transformation, tumor progression, and response to treatment [ 22 ], we review in this article the evidence implicating NAD + and its metabolites as regulators of calcium channels, and the function of these ion channels in cancer, aiming to shed light on the mechanisms of NAD + metabolites related to calcium signaling in tumorigenesis, metastasis, and therapy. At the same time, this review is also to thank Professor Barry V. L. Potter for his great contribution in this research field over the years.…”