Expression profile and functional role of S100A14 in human cancer

Abstract

S100A14 is one of the new members of the multi-functional S100 protein family. Expression of S100A14 is highly heterogeneous among normal human tissues, suggesting that the regulation of S100A14 expression and its function may be tissueand context-specific. Compared to the normal counterparts, S100A14 mRNA and protein levels have been found to be deregulated in several cancer types, indicating a functional link between S100A14 and malignancies. Accordingly, S100A14 is functionally linked with a number of key signaling molecules such as p53, p21, MMP1, MMP9, MMP13, RAGE, NF-kB, JunB, actin and HER2. Of interest, S100A14 seems to have seemingly opposite functions in malignancies arising from the gastrointestional tract (tissues rich in epithelial components) compared to cancers in the other parts of the body (tissues rich in mesenchymal components). The underlying mechanism for these observations are currently unclear and may be related to the relative abundance and differences in the type of interaction partners (effector protein) in different cancer types and tissues. In addition, several studies indicate that the expression pattern of S100A14 has a potential to be clinically useful as prognostic biomarker in several cancer types. This review attempts to provide a comprehensive summary on the expression pattern and functional roles/related molecular pathways in different cancer types. Additionally, the prognostic potential of S100A14 in the management of human malignancies will be discussed.