S100A4 promotes endometrial cancer progress through epithelial-mesenchymal transition regulation

Abstract

Epithelial-mesenchymal transition (EMT) is a major cause of endometrial cancer (EC) to initiate invasion and metastasis. S100A4, a calcium-binding protein, is implicated in multistage of tumorigenesis and tumor progression. The correlation between S100A4 and EMT in EC is still unclear. This study was aimed to clarify the role of S100A4 in EC and the relationship between S100A4 expression and EMT markers. S100A4, E-cadherin, and vimentin were detected in tissues of EC patients (n=50) by immunohistochemistry. The impact of S100A4 on EC cell proliferation, migration and invasion was investigated via RNA interference, and the correlation between S100A4 and EMT markers were also explored. The results showed that S100A4 was significantly increased in epithelial cells of EC compared with the normal endometrium (P<0.05), also S100A4 level was positively related to age (P=0.021), histological grade (P<0.001), and lymph node metastasis (P<0.001). Additionally, silencing of S100A4 remarkably attenuated EC cell migration and invasion. Significant morphological change accompanied with the downregulation of EMT markers, E-cadherin and vimentin were also observed. Aberrant S100A4 expression may predict EC progression and play an important role in regulating EC cell invasion through EMT regulation. Hence, S100A4 is a promising therapeutic target.

Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

“…It has been demonstrated that S100A4 can stimulate cancer cell migration and invasion by direct S100A4 and myosin-IIA interactions [106] or S100A4-induced MMPs secretion [107]. It has also been shown that S100A4 can induce EMT, promoting a mesenchymal, more-motile phenotype in cancer cells [108]. Lately, the ability of extracellular S100A4 to act on stromal cells and participate in tumor -stroma interactions has been addressed.…”

Cancer‑associated fibroblasts induce epithelial‑mesenchymal transition through secreted cytokines in endometrial cancer cells

“…Treatment with Janus kinase- and Signal transducer and activator of transcription 3-specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell proliferation ( 27 ); also, aberrant S100A4 expression may predict EC progression and serve an important role in regulating EC cell invasion through EMT regulation. Therefore, S100A4 is a promising therapeutic target ( 28 ). In the present study, only four growth factors were studied; a more comprehensive analysis will be included in our future studies.…”

“…Tumor growth depends on interactions between multiple inter-dependent cell types, among these different cell types, CAFs are becoming a topic of study as recipients and as producers of pro-tumorigenic signals ( 29 ). There are a number of previous studies concerning the role of CAFs and their mechanisms of action in various tumors ( 27 , 28 , 30 , 31 ). Hwang et al ( 32 ) examined pancreatic cancer, and identified that cancer-associated stromal fibroblasts exhibited an important role in supporting and promoting growth and metastasis in pancreatic cancer.…”

“…The results provide a novel perspective for the treatment of endometrial cancer through cytokines. Previous articles ( 28 – 30 ) have not examined CAFs by describing and analyzing their cytokine expression profiles, which is the primary focus of the present study. The data suggest that CAFs may induce EMT through secreted cytokines in endometrial cancer cells.…”

The suppressive role of calcium sensing receptor in endometrial cancer

“…Tissue specimens were obtained from patients who had been diagnosed with endometrial cancer (n = 50) and from normal endometria (n = 10) as previously described 29 . All patients had undergone surgical resections or biopsies at Wuhan Union Hospital between 2010 and 2013, and the diagnoses were confirmed by a gynaecologic pathologist.…”