AUTHOR=Tajada Sendoa , Villalobos Carlos 

TITLE=Calcium Permeable Channels in Cancer Hallmarks

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00968

DOI=10.3389/fphar.2020.00968

ISSN=1663-9812

ABSTRACT=Cancer, the second cause of death worldwide, is characterized by several common criteria, known as the “cancer hallmarks” including unrestrained cell proliferation, cell death resistance, invasion and metastasis, and angiogenesis. Ca2+ permeable channels are proteins present in external and internal biological membranes, diffusing Ca2+ ions down their electrochemical gradient. Numerous physiological functions are mediated by Ca2+ channels, ranging from Ca2+ homeostasis to sensory transduction. Consequently, Ca2+ channels play important roles in human physiology and it is not a surprise the increasing number of evidences connecting Ca2+ channels disorders with tumor cells growth, survival and migration. Multiple studies suggest that Ca2+ signals are augmented in various cancer cell types, contributing to cancer hallmarks. This review focuses in the role of Ca2+ permeable channels signaling in cancer with emphasis on the mechanisms behind the remodeling of the Ca2+ signals. The Store-Operated Channels (SOC) and Transient Receptor Potential (TRP) channels are the main extracellular Ca2+ source in the plasma membrane of non-excitable cells, while inositol trisphosphate receptors (IP3R) are the main channels releasing Ca2+ from the endoplasmic reticulum (ER). Alterations in the activity and/or expression of these Ca2+ channels, as wells as, the Ca2+ buffering by mitochondria affect intracellular Ca2+ homeostasis and signaling, contributing to the transformation of normal cells into their tumor counterparts. Several compounds reported to counteract several cancer hallmarks also modulate the activity and/or the expression of these channels including non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and sulindac, and inhibitors of polyamine biosynthesis, like difluoromethylornithine (DFMO). The possible role of the Ca2+ permeable channels targeted by these compounds in cancer and their action mechanism will be discussed also in the review.