Abstract
S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial–mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.
Highlights
Cervical cancer is the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases in 2012 [1]
S100A7 expression was increased in high grade cervical intraepithelial neoplasm (CIN) compared with cervical cancer (P < 0.01) (Figure 1B)
We performed IHC analysis of S100A7 in normal cervical tissue, cervical cancer and CIN and found www.impactjournals.com/oncotarget that the staining of S100A7 was scattered, suggesting that S100A7 displays the cellular heterogeneity in cervical cancers, which is supported by previous study that S100A7 exhibits heterogeneous and inducible characteristic in squamous cell carcinomas (SCC) [24]
Summary
Cervical cancer is the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases in 2012 [1]. Human papillomavirus (most notably HPV16 and HPV18) have been definitely defined human carcinogens and their persistent infection in the cervix is established as a necessary cause for cervical cancer [2]. Only a small fraction of infections that persist may progress to cervical cancer, indicating that many other factors contribute to the progression of cervical cancer. Diverse factors secreted by the cancer cells and host cells in their local microenvironments may trigger the molecular events that are associated with the EMT program [3]. A number of findings indicate that multiple molecules were involved in the regulation of EMT in cervical cancer.
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