| Cervical cancer is a great threaten to women's health and is the second factor contributed to women death.The metastasis followed the relapse of cervical cancer are still the most tough problem encountered in its treatments,which is also the major cause of death and treatments failure in cervical cancer.It is widely accepted that persistent infection of high-risk human papillomavirus(Hr-HPV)is the main cause of cervical cancer.Recently,although the development of screening strategies and the application of HPV preventive vaccines,the occurrence and mortality of cervical cancer in developed countries is decreased significantly.So to further elucidate process and mechanism of cervical cancer progression is the cornerstone of developing new therapeutic strategies.Epithelial-mesenchymal transition(EMT)is the main reason leading to tumor metastasis and plays an important role in cervical cancer progression.Previous studies indicated that EMT involved in the process of embryonic development and organogenesis,chronic inflammation,tumor invasion and formation.In addition,EMT plays an important role in cervical cancer metastasis and progression.A variety of factors in vivo or vitro can lead to the occurrence of EMT in cervical cancer,including hypoxia,HPV infection,activation of oncogenes and the inbalance of cervical microenvironment.These factoers could swith on the programme of EMT and promote migration in cervical cancer through activating EMT-related transcription factors.The S100 protein family belongs to the largest subgroup of calcium binding EF-hand type proteins.These proteins have been reported to be involved in a range of biological functions that is related both to normal development and tumorigenesis.S100A14 is a distinct member of the family involved in several functional and pathological processes.Upregulation of S100A14 has been documented in a variety of tumors,including lung,ovarian,and breast tumors,while loss of S100A14 expression has been illustrated in tumors of the colon,rectum,kidney,oral and esophageal squamous cell carcinoma and small intestinal adenocarcinoma.Recent studies showedthat the expression of S100A14 was downregulated in esophageal squamous cell carcinomas(ESCC).S100A14 induces cell cycle arrest,apoptosis or metastasis in ESCC,and regulates these processes in a receptor for advanced glycation end-products(RAGE)-dependent manner.we also found that S100A14 promoted breast cancer cell motility in a p53 or Her2-dependent manner.However,the potential clinical significance and biological functions of S100A14 in cervical cancer has not yet been clarified.In this study,we firstly examined the correlation between S100A14 expression and clinical-pathological parameters in cervical cancers.Next,we observed the effect of S100A14 on cell cycle progression,cell proliferation,migration and invasion by employing lentiviral-mediated overexpression and knockdown of S100A14 in cervical cancer cells.Furthermore,we investigated the underlying mechanism of S100A14 affecting cell migration and invasion.Immunohistochemistry analysis demonstrated that S100A14 expression was associated with the International Federation of Gynecology and Obstetrics(FIGO)stage(P=0.025)and lymph node(LN)metastasis(P=0.001).Functional assays showed that S100A14 overexpression increased the proportion of G2/M phase,promoted cell proliferation,migration,and invasion,whereas S100A14 knockdown exhibited adverse effect on above properties.Mechanistic investigation demonstrated that S100A14 can act as a mediator of epithelialmesenchymal transition(EMT).And overexpression of S100A14 increased expression of N-cadherin and Vimentin while decreased expression of E-cadherin.The opposite results were observed in S100A14-silenced cells.Taken together,our data indicate that S100A14 has a crucial role in cervical cancer progression.This study significantly increases our understanding of S100A14 functional roles in cervical cancer,which may lead to the development of a novel therapeutic target for cervical cancer. |
PDF Full Text Request