Calcium signalling and cancer cell growth

Abstract

Abstract:Cancer is caused by defects in the mechanisms underlying cell proliferation and cell death. Calcium ions are central to both phenomena, serving as major signalling agents with spatial localization, magnitude and temporal characteristics of calcium signals ultimately determining cell's fate. There are four primary compartments: extracellular space, cytoplasm, endoplasmic reticulum and mitochondria that participate in the cellular Ca 2+ circulation. They are separated by own membranes incorporating divers Ca 2+ -handling proteins whose concerted action provides for Ca 2+ signals with the spatial and temporal characteristics necessary to account for specific cellular response. The transformation of a normal cell into a cancer cell is associated with a major re-arrangement of Ca 2+ pumps, Na/Ca exchangers and Ca 2+ channels, which leads to the enhanced proliferation and impaired ability to die. In the present chapter we examine what changes in Ca 2+ signalling and the mechanisms that support it underlie the passage from normal to pathological cell growth and death control. Understanding this changes and identifying molecular players involved provides new prospects for cancers treatment

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

“…34,35 Bikle et al 35 showed that squamous cell carcinoma cell lines failed to respond to the prodifferentiating actions of vitamin D. Alterations of calcium signaling have also been linked to carcinomas of breast, colon, esophagus, liver, ovarian, and prostate origin. [27][28][29]33,36,37 These findings suggest a strong association between disruptions of calcium signaling and carcinogenesis and may provide targets for future therapeutic interventions by targeting of these pathways.…”

“…Calcium homeostasis is important in the orderly progression of the cell cycle, regulation of cell proliferation and growth, and apoptosis. 27 Deregulation of these intricate calcium signaling pathways has been implicating in tumorigenesis by evasion of apoptosis and the acquisition of self-sustaining growth signals. 27 The mechanisms of the deregulation of calcium signaling have been shown through T-type calcium channels, calcium pumps/exchangers, vitamin D, and calcium-sensing receptors.…”

“…27 Deregulation of these intricate calcium signaling pathways has been implicating in tumorigenesis by evasion of apoptosis and the acquisition of self-sustaining growth signals. 27 The mechanisms of the deregulation of calcium signaling have been shown through T-type calcium channels, calcium pumps/exchangers, vitamin D, and calcium-sensing receptors. [27][28][29][30][31][32][33] Calcium and vitamin D pathways have been found to be especially important in activating the genetic pathways required for keratinocyte differentiation.…”

“…27 The mechanisms of the deregulation of calcium signaling have been shown through T-type calcium channels, calcium pumps/exchangers, vitamin D, and calcium-sensing receptors. [27][28][29][30][31][32][33] Calcium and vitamin D pathways have been found to be especially important in activating the genetic pathways required for keratinocyte differentiation. 34,35 Bikle et al 35 showed that squamous cell carcinoma cell lines failed to respond to the prodifferentiating actions of vitamin D. Alterations of calcium signaling have also been linked to carcinomas of breast, colon, esophagus, liver, ovarian, and prostate origin.…”

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

“…The CaR is an essential part of an intricate network of Ca 2 þ -signalling pathways that control normal and cancer cell growth (Capiod et al, 2007). Depending on cell-specific coupling to appropriate G-proteins, activation of the CaR by elevated extracellular Ca 2 þ reduces the rate of cellular proliferation, as seen in human colon carcinoma (Kallay et al, 2003;Chakrabarty et al, 2005) or ovarian surface epithelial cells (Bilderback et al, 2002), but may also stimulate cell growth, as seen in malignant Leydig cells , and protect from apoptosis, for example, in prostate cancer cells (Lin et al, 1998).…”