Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration

Abstract

The study of calcium channels in molecular mechanisms of cancer transformation is still a novel area of research. Several studies, mostly conducted on cancer cell lines, however support the idea that a diversity of plasma membrane channels participates in the remodeling of Ca2+ homeostasis, which regulates various cancer hallmarks such as uncontrolled multiplication and increase in migration and invasion abilities. However few is still understood concerning the intracellular signaling cascades mobilized by calcium influx participating to cancer cell behavior. This review intends to gather some of these pathways dependent on plasma membrane calcium channels and described in prostate, breast and lung cancer cell lines. In these cancer cell types, the calcium channels involved in calcium signaling pathways promoting cancer behaviors are mostly non-voltage activated calcium channels and belong to the TRP superfamily (TRPC, TPRPV and TRPM families) and the Orai family. TRP and Orai channels are part of many signaling cascades involving the activation of transmembrane receptors by extracellular ligand from the tumor environment. TRPV can sense changes in the physical and chemical environment of cancer cells and TRPM7 are stretch activated and sensitive to cholesterol. Changes in activation and or expression of plasma-membrane calcium channels affect calcium-dependent signaling processes relevant to tumorigenesis. The studies cited in this review suggest that an increase in plasma membrane calcium channel expression and/or activity sustain an elevated calcium entry (constitutive or under the control of extracellular signals) promoting higher cell proliferation and migration in most cases. A variety of non-voltage-operated calcium channels display change expression and/or activity in a same cancer type and cooperate to the same process relevant to cancer cell behavior, or can be involved in a different sequence of events during the tumorigenesis. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Overexpression of calcyphosine is associated with poor prognosis in esophageal squamous cell carcinoma

“…In a study concerning prostate cancer, data revealed that transient receptor potential cation channel subfamily V member 6-dependent Ca 2+ influx contributed to prostate cancer development by enhancing proliferation of tumor cells and protecting them from apoptosis (26). Other studies demonstrated that higher plasma membrane channel expression and Ca 2+ influx were associated with increased proliferation and tumor cell migration (27,28). Therefore, we hypothesized that CAPS may promote tumorigenesis and tumor progression by disturbing intracellular Ca 2+ homeostasis.…”

Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel

“…The activation of intracellular Ca 2þ effectors in turn regulates cellular activities necessary for cell-cycle progression and cell proliferation (5,9). Abnormal expression and activity of Ca 2þ signaling proteins have been suggested to contribute to the highly proliferative capacity of several human cancers (7,9). These include members of the transient receptor potential (TRP) superfamily, which form Ca 2þ entry channels.…”

“…When stimulated by extracellular calcium ([Ca 2þ ] o ), CaSR acts through at least two G protein pathways (Gq/ 11 and Gi/o) to regulate cell signaling, including increases in cytosolic Ca 2þ concentration ([Ca 2þ ] cyt ), which can result from Ca 2þ release from internal stores or Ca 2þ entry from extracellular space through Ca 2þ -permeable cation channels. The activation of intracellular Ca 2þ effectors in turn regulates cellular activities necessary for cell-cycle progression and cell proliferation (5,9). Abnormal expression and activity of Ca 2þ signaling proteins have been suggested to contribute to the highly proliferative capacity of several human cancers (7,9).…”

Emerging Role of Ca_V1.2 Channels in Proliferation and Migration in Distinct Cancer Cell Lines

“…Channelopathies are involved in a wide range of diseases including epilepsy, migraine, blindness, hypertension, and cardiac arrhythmia [4] . Likewise, ion channel malfunction has been suggested to be involved in altered cell proliferation, migration, apoptosis, and differentiation [1,2,[5][6][7] .…”