This review summarized up to date advancement on the role of S100A4 in human cancer development, progression, and metastasis and the underlying molecular events and then strategies to target S100A4 expression experimentally.
We then knocked down of S100A4 expression by RNA interference (S100A4 siRNA) and investigated its effects on growth and metastasis in two human ATC cell lines 8505C (BRAFV600E) and Cal-62 (BRAFwt) in vitro and in vivo.
S100 calcium binding protein A4 (S100A4) and cysteine-rich angiogenic inducer 61 (CYR61) play important roles in epithelial-mesenchymal-transition (EMT), invasion and metastasis by promoting cancer cell motility.
We found that CNE-1-S100A4 showed significantly increased invasion ability as compared to the controls both in vitro and in vivo, which indicated that S100A4 induced EMT occurrence and promoted metastasis.
In contrast, S100a4 epithelial overexpression in Apc<sup>1638N/+</sup>/KRAS<sup>V12G</sup> mice increases the dissemination of intestinal tumour cells to the liver, in agreement with its role in tumour metastasis.
The calcium-binding S100A4 protein is involved in epithelial to mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity, mobility and metastasis of cancer cells.
S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells.
In metastatic breast cancers, NFAT5 promotes epithelial-mesenchymal transition (EMT) and invasion of cells by switching on the expression of the calcium binding protein S100A4, and facilitates the angiogenesis of breast epithelial cells and thus the development of metastases by transcriptionally activating vascular endothelial growth factor C (VEGF-C).
Upregulation of the metastasis-promoting S100A4 protein has been linked to tumor migration and invasion, and clinical studies have demonstrated that significant expression of S100A4 in primary tumors is indicative of poor prognosis.