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.

Keywords: (4-[3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-4,5-dihydro-pyrazol-1-yl]-benzoic acid; (4-[3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-4,5-dihydro-pyrazol-1-yl]-phenyl)-(4-methyl-piperazin-1-yl)-methanone; (−) enantiomer of dihydropyrine 3-methyl-5-3-(4,4-diphenyl-1-piperidinyl)-propyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-piridine-3,5-dicarboxylate-hydrochloride (niguldipine); 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine; 12-O-tetradecanoyl-phorbol-13-acetate; 2-chloro-(ε-amino-Lys(75))-[6-(4-(N,N′-diethylaminophenyl)-1,3,5-triazin-4-yl]-CaM adduct; 3′-(β-chloroethyl)-2′,4′-dioxo-3,5′-spiro-oxazolidino-4-deacetoxy-vinblastine; 7,12-dimethylbenz[a]anthracene; Apoptosis; Autophagy; B859-35; CAPP(1)-CaM; Ca(2+) binding protein; Calmodulin; Cancer biology; Cell proliferation; DMBA; EBB; FL-CaM; FPCE; HBC; HBCP; J-8; KAR-2; KN-62; KN-93; N-(4-aminobutyl)-2-naphthalenesulfonamide; N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; N-(6-aminohexyl)-1-naphthalenesulfonamide; N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; N-8-aminooctyl-5-iodo-naphthalenesulfonamide; N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide; O-(4-ethoxyl-butyl)-berbamine; RITC-CaM; TA-CaM; TFP; TPA; W-12; W-13; W-5; W-7; fluorescein-CaM adduct; fluphenazine-N-2-chloroethane; norchlorpromazine-CaM adduct; rhodamine isothiocyanate-CaM adduct; trifluoperazine.