S100P, a peculiar member of S100 family of calcium-binding proteins implicated in cancer

Abstract

S100P belongs to several members of the S100 family of calcium-binding proteins, associated with malignant phenotype. Altered levels of S100P expression have been described at different stages and types of cancer. Transcriptional regulation involves different pathways activated by glucocorticoids, growth factors and bone morphogenic factor via the corresponding receptors. Signals coming from these pathways appear to be transmitted through ERK1/2 (extracellular-signal regulated kinase) and mediated presumably by STAT, SMAD, NFkB transcription factors. The secreted form of S100P can bind to extracellular ligand-binding site of RAGE (receptor for advanced glycation end-products), and via activation of ERK/MAPK pathway can influence gene expression, cell proliferation and survival. In addition, S100P interacts and modulates the activity of several targets with multiple binding modes and simultaneous coordination of further target proteins in larger multiprotein complexes, e.g. scaffolding proteins -IQGAP1 and ezrin, known to promote and regulate signal transduction pathways. The majority of S100P binding partners are proteins involved in cytoskeletal dynamics, and their physical interactions with S100P lead to defects in cellular morphogenesis and tissue disruption, the acquisition of uncontrolled migratory and invasive features. Finally, the evidence for S100P role in cancer metastasis opens a new direction for the future research efforts.