Deciphering the Role of Ca(2+) Signalling in Cancer Metastasis: From the Bench to the Bedside

SIMPLE SUMMARY: Ca(2+) dyshomeostasis is implicated in several key pathophysiological processes attributed to cancer metastasis biology. Here, we decipher the role of intracellular and extracellular Ca(2+) signalling pathways in processes that contribute to metastasis at the local level (involving cell proliferation, adhesion, motility, invasion, migration and the epithelial-mesenchymal transition) and also their effects on cancer metastasis globally. Ca(2+) proteins are potential candidates for cancer biomarkers and druggable targets for future metastatic cancer therapy. ABSTRACT: Metastatic cancer is one of the major causes of cancer-related mortalities. Metastasis is a complex, multi-process phenomenon, and a hallmark of cancer. Calcium (Ca(2+)) is a ubiquitous secondary messenger, and it has become evident that Ca(2+) signalling plays a vital role in cancer. Ca(2+) homeostasis is dysregulated in physiological processes related to tumour metastasis and progression—including cellular adhesion, epithelial–mesenchymal transition, cell migration, motility, and invasion. In this review, we looked at the role of intracellular and extracellular Ca(2+) signalling pathways in processes that contribute to metastasis at the local level and also their effects on cancer metastasis globally, as well as at underlying molecular mechanisms and clinical applications. Spatiotemporal Ca(2+) homeostasis, in terms of oscillations or waves, is crucial for hindering tumour progression and metastasis. They are a limited number of clinical trials investigating treating patients with advanced stages of various cancer types. Ca(2+) signalling may serve as a novel hallmark of cancer due to the versatility of Ca(2+) signals in cells, which suggests that the modulation of specific upstream/downstream targets may be a therapeutic approach to treat cancer, particularly in patients with metastatic cancers.