S100 proteins and their influence on pro-survival pathways in cancer.
The S100 gene family is composed of at least 20 members that share a common structure defined in part by the Ca2+ binding EF-hand motif. These genes which are expressed in a discriminate fashion in specific cells and tissues, have been described to have either an intracellular or extracellular function, or both. S100 proteins are implicated in the immune response, differentiation, cytoskeleton dynamics, enzyme activity, Ca2+ homeostasis and growth. A potential role for S100 proteins in neoplasia stems from these activities and from the observation that several S100 proteins have altered levels of expression in different stages and types of cancer. While the precise role and importance of S100 proteins in the development and promotion of cancer is poorly understood, it appears that the binding of Ca2+ is essential for exposing amino acid residues that are important in forming protein-protein interactions with effector molecules. The identity of some of these effector molecules has also now begun to emerge, and with this the elucidation of the signaling pathways that are modulated by these proteins. Some of these interactions are consistent with the diverse functions noted above. Others suggest that, many S100s may also promote cancer progression through specific roles in cell survival and apoptosis pathways. This review summarizes these findings and their implications.
Manitoba Institute of Cell Biology, Winnipeg, Canada.
Ethan D
ED
Emberley
Leigh C
LC
Murphy
Peter H
PH
Watson
D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002462:Cell Membrane; D002470:Cell Survival; D002630:Chemotactic Factors / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009414:Nerve Growth Factors; D000075383:S100 Calcium Binding Protein A6; D000075023:S100 Calcium Binding Protein A7; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000502:physiology*
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002630:Chemotactic Factors; D009414:Nerve Growth Factors; D000075383:S100 Calcium Binding Protein A6; D000075023:S100 Calcium Binding Protein A7; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C098997:S100A2 protein, human; C089242:S100A7 protein, human; C055351:S100A6 protein, human; C077591:S100A4 protein, human; D002118:Calcium