S100A4 is a known mediator of EMT, leading to metastasis and EMT has been proposed as a potential source of cancer-associated fibroblastic cells in solid tumors.
Here, we found that S100 calcium-binding protein A4 (S100A4), a major metastasis-promoting protein, confers metabolic plasticity to drive tumor invasion and metastasis of non-small cell lung cancer cells.
Our data demonstrate that the S100A4 gene controls the invasive potential of human CaP cells through regulation of MMP-9 and that this association may contribute to metastasis of CaP cells.
The structure of the active form of S100A4 provides insight into its interactions with its binding partners and a better understanding of its role in metastasis.
The consequences are intriguing, connecting the metastasis-promoting protein S100A4 to the large set of important p53-mediated functions, with broad potential importance in cancer development and metastasis.
These results identify the amino acids of S100A4 that are involved in metastasis induction and show that the C-terminal region of S100A4 is a possible target for inhibitors of its metastatic action.
To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea.
OPN is, as S100A4, known to result in a variety of cellular effects potentially leading to increased angiogenesis and metastasis, and several of the activated signaling pathways are common for the two proteins.
The functional importance of stromal Tenascin-C and S100A4(+) fibroblast-derived VEGF-A in metastasis was established by examining Tenascin-C null mice and transgenic mice expressing Cre recombinase under control of the S100A4 promoter crossed with mice carrying VEGF-A alleles flanked by loxP sites, which exhibited a significant decrease in metastatic colonization without effects on primary tumor growth.
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.
These findings suggest that S100A4 protects gastric cancer cells from anoikis by regulation of αv and α5 integrin expression, which sheds a novel light for the role of S100A4 in cancer metastasis.
Focusing on S100A4, S100A8 and S100A9, in this review we discuss the role these proteins play in primary tumors and in the development of metastases, in particular during the formation of pre-metastatic niches.
S100A4 is a well established marker and mediator of metastatic disease, but the exact mechanisms responsible for the metastasis promoting effects are less well defined.