The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer

Abstract

Calmodulin (CaM) is a ubiquitous Ca(2+) receptor protein mediating a large number of signaling processes in all eukaryotic cells. CaM plays a central role in regulating a myriad of cellular functions via interaction with multiple target proteins. This review focuses on the action of CaM and CaM-dependent signaling systems in the control of vertebrate cell proliferation, programmed cell death and autophagy. The significance of CaM and interconnected CaM-regulated systems for the physiology of cancer cells including tumor stem cells, and processes required for tumor progression such as growth, tumor-associated angiogenesis and metastasis are highlighted. Furthermore, the potential targeting of CaM-dependent signaling processes for therapeutic use is discussed.

The activating role of phospho-(Tyr)-calmodulin on the epidermal growth factor receptor

“…The transient increase in the concentration of cytosolic free Ca 2 + upon cell stimulation by hormones or mitogenic factors favours the formation of the Ca 2 + -CaM complex [50], in turn regulating a myriad of CaM-dependent proteins [10][11][12][13]. Nevertheless, it is reasonable to assume that Ca 2 + may not be the only signal with the capacity to modulate the CaM-dependent systems in the cell.…”

“…Calmodulin (CaM) is a Ca 2 + -receptor protein that transduces Ca 2 + -mediated signals by binding to and regulating the activity of hundreds of enzymes and non-enzymatic proteins, thereby controlling a myriad of cellular functions [10][11][12][13]. EGFR signalling induces an early and transient increase in the cytosolic concentration of free Ca 2 + [14][15][16], which results in the formation of the Ca 2 + -CaM complex.…”

Effect of three calmodulin antagonists on subpopulations of CD44/CD24 immunophenotypes in breast cancer cell lines

“…Calmodulin antagonists have antitumor activities against various cancers which could be explained by the role of calmodulin in raising the rate of cell growth and degree of tumor malignancy [12].…”

A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ

“…CALM is a calcium receptor protein that regulates a multitude of cellular functions including proliferation, apoptosis, autophagy, proliferation, differentiation and cell migration, cell adhesion and angiogenesis (19). It operates by sequestering calcium in the cell, thus allowing for transient changes in ionized calcium across the cell cytosol to the nucleus as part of many cell signalling pathways (19). Its marked increase in the MM secretome is indicative of the many cell signalling pathways that are activated in MM and associated with many of the pathways discussed below.…”