Abstract
S100A4, a Mediator of Metastasis
Highlights
The transition from benign tumor growth to malignancy is manifested by the ability of tumor cells to traverse tissue barriers and invade surrounding tissues
The orientation of helices 3 and 4 in the S100A4 typical EF-hand is similar to only one other member of the S100 protein family, S100A6 [11], and less like other S100 family members for which three-dimensional structures are available in the calcium-free state [12, 13]
The “hinge region” and the C-terminal loop of S100 proteins are involved in target protein binding; the lack of sequence homology in these regions provides a means for S100 proteins to interact with specific binding partners [14]
Summary
The majority of the human, mouse, and rat S100 genes, including S100A4, are located as a gene cluster on chromosomes 1q21, 3f3, and 2q34, respectively [56]. The human S100A4 gene contains 4 exons, and the additional exon is located within the 5Ј-UTR and is noncoding. The two splice variants display different expression profiles in human tissues and tumor cell lines [57]; the significance of this observation with respect to gene or protein activity is not known. Recent studies show that following orthotopic injection of a highly metastatic, S100A4-positive, carcinoma cell line into S100A4Ϫ/Ϫ mice, tumor development and the formation metastases are suppressed [68]. These observations suggest that S100A4 expression in host-derived stroma may contribute to tumor progression and metastasis
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