Abstract
Simple SummaryCa2+ dyshomeostasis is implicated in several key pathophysiological processes attributed to cancer metastasis biology. Here, we decipher the role of intracellular and extracellular Ca2+ 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. Ca2+ proteins are potential candidates for cancer biomarkers and druggable targets for future metastatic cancer therapy.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 (Ca2+) is a ubiquitous secondary messenger, and it has become evident that Ca2+ signalling plays a vital role in cancer. Ca2+ 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 Ca2+ 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 Ca2+ 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. Ca2+ signalling may serve as a novel hallmark of cancer due to the versatility of Ca2+ 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.
Highlights
Cancer is a serious public health condition globally
The findings show that binding of these proteins to the calcium-sensing receptor (CaSR) initiates intracellular Ca2+ signaling cascades which lead to the bone metastasis of multiple cancers, indicating that the CaSR can be a treatment target and a diagnostic indicator of metastasis to bone
While navigating clinicaltrials.gov, we found a paucity of clinical studies using changes in Ca2+ signalling pathways as a detection approach for metastatic cancer or targeting Ca2+ proteins as an adjuvant therapeutic approach for patients with metastatic cancer
Summary
Cancer is a serious public health condition globally. Metastasis is a significant hallmark of cancer, defined as the transition of cancer cells from their original site to another site, and accounts for ~90% of cancer-related mortalities [1]. Metastasis is a complex phenomenon that involves multiple phases (from the translocation from the primary site to the colonization of the secondary site) and several pathophysiological processes (including cell proliferation, adhesion and motility; tumour invasion and migration; angiogenesis; and the epithelial-mesenchymal transition) which interact with each other at a local level to develop metastatic cancer at a global level. It is a fundamental phenomenon in our understanding of the underlying molecular mechanisms related to cancer pathogenesis; it is a viable target for cancer therapy and approaches to prevent and target metastatic cancer have drawn scientific attention for several decades and remain of great interest in decoding cancer biology.
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