Crosstalk between Ca2+ Signaling and Cancer Stemness: The Link to Cisplatin Resistance

Abstract

In the fight against cancer, therapeutic strategies using cisplatin are severely limited by the appearance of a resistant phenotype. While cisplatin is usually efficient at the beginning of the treatment, several patients endure resistance to this agent and face relapse. One of the reasons for this resistant phenotype is the emergence of a cell subpopulation known as cancer stem cells (CSCs). Due to their quiescent phenotype and self-renewal abilities, these cells have recently been recognized as a crucial field of investigation in cancer and treatment resistance. Changes in intracellular calcium (Ca2+) through Ca2+ channel activity are essential for many cellular processes such as proliferation, migration, differentiation, and survival in various cell types. It is now proved that altered Ca2+ signaling is a hallmark of cancer, and several Ca2+ channels have been linked to CSC functions and therapy resistance. Moreover, cisplatin was shown to interfere with Ca2+ homeostasis; thus, it is considered likely that cisplatin-induced aberrant Ca2+ signaling is linked to CSCs biology and, therefore, therapy failure. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to a range of pressures dictates the global degree of cisplatin resistance. However, if we can understand the molecular mechanisms linking Ca2+ to cisplatin-induced resistance and CSC behaviors, alternative and novel therapeutic strategies could be considered. In this review, we examine how cisplatin interferes with Ca2+ homeostasis in tumor cells. We also summarize how cisplatin induces CSC markers in cancer. Finally, we highlight the role of Ca2+ in cancer stemness and focus on how they are involved in cisplatin-induced resistance through the increase of cancer stem cell populations and via specific pathways.

Adaptive Immune Resistance in Cancer Therapy

“…The resistance mechanism of cisplatin is very complex, and its resistance is often related to "drug pump" proteins, molecular detoxification, DNA damage repair, and activation of certain pathways (Amable, 2016). Some previous studies have begun to focus on the mechanism of cisplatin resistance and potential intervention targets (Wang et al, 2021;Kouba et al, 2022;. Here, we found that PCDH7 may be involved in cisplatin resistance in lung cancer through public database analysis (GSE21656 and GSE108214).…”

Integrative analysis illustrates the role of PCDH7 in lung cancer development, cisplatin resistance, and immunotherapy resistance: an underlying target

“…The resistance mechanism of cisplatin is very complex, and its resistance is often related to “drug pump” proteins, molecular detoxification, DNA damage repair, and activation of certain pathways ( Amable, 2016 ). Some previous studies have begun to focus on the mechanism of cisplatin resistance and potential intervention targets ( Wang et al, 2021 ; Kouba et al, 2022 ; Shi et al, 2022 ). Here, we found that PCDH7 may be involved in cisplatin resistance in lung cancer through public database analysis (GSE21656 and GSE108214).…”

Research Progress of Resveratrol in Oral Cancer

“…Calcium ion (Ca2+) involved in the regulation of cells a variety of important life activities, intracellular stable Ca2+ concentration is the premise and the basis of maintaining behavior function, in the process of autophagy apoptosis, Ca2+ also plays an important role [23], Taiwan scholars [24] proved that 20-40 mM resveratrol induced oral cancer OC2 cells, resveratrol through PKC and PLC pathway, cause the endoplasmic reticulum release Ca2+, inducing cell apoptosis.…”