title: S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence.
abstract: The fatality of cancer is mainly bestowed to the property of otherwise benign tumor cells to become malignant and invade surrounding tissues by circumventing normal tissue barriers through a process called metastasis. S100A4 which is a member of the S100 family of calcium-binding proteins has been shown to be able to activate and integrate pathways both intracellular and extracellular to generate a phenotypic response characteristic of cancer metastasis. A large number of studies have shown an increased expression level of S100A4 in various types of cancers. However, its implications in cancer metastasis in terms of whether an increased expression of S100A4 is a causal factor for metastasis or just another after effect of several other physiological and molecular changes in the body resulting from metastasis are not clear. Here we describe the emerging preclinical and clinical evidences implicating S100A4 protein, in both its forms (intracellular and extracellular) in the process of tumorigenesis and metastasis in humans. Based on studies utilizing S100A4 as a metastasis biomarker and molecular target for therapies such as gene therapy, we suggest that S100A4 has emerged as a promising molecule to be tested for anticancer drugs. This review provides an insight in the (1) molecular mechanisms through which S100A4 drives the tumorigenesis and metastasis and (2) developments made in the direction of evaluating S100A4 as a cancer biomarker and drug target.
authors: Department of Molecular Chemoprevention and Therapeutics, University of Minnesota, Austin, MN 55912, USA.
authors: Shrawan Kumar
authors: SK
authors: Mishra
authors: Hifzur Rahman
authors: HR
authors: Siddique
authors: Mohammad
authors: M
authors: Saleem
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D011485:Protein Binding; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human