title: HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo.
abstract: OBJECTIVE
  Cadherin switch, as a key hallmark of epithelial-mesenchymal transition (EMT), is characterized by reduced E-cadherin expression and increased N-cadherin or P-cadherin expression, and has been implicated in many aggressive tumors, but the importance and regulatory mechanism of cadherin switch in cervical cancer have not been investigated. Our study aimed to explore the role of cadherin switch by regulation of HPV-16 E6/E7 in progression and metastasis of cervical cancer.
  
  
  METHODS
  The expressions of E-cadherin and P-cadherin were examined by immunohistochemical staining in 40 cases of high-grade cervical lesions with HPV-16 infection only in which HPV-16 E6 and E7 expression had been detected using qRT-PCR method. Through modulating E6 and E7 expression using HPV-16 E6/E7 promoter-targeting siRNAs or expressed vector in vitro, cell growth, migration, and invasion were separately tested by MTT, wound-healing and transwell invasion assays, as well as the expressions of these cadherins by western blot analyses. Finally, the expressions of these cadherins in cancerous tissues of BALB/c-nu mouse model inoculated with the stable HPV-16 E6/E7 gene silencing Siha and Caski cells were also measured by immunohistochemical staining.
  
  
  RESULTS
  Pearson correlation coefficient analyses showed the strongly inverse correlation of E-cadherin expression and strongly positive correlation of P-cadherin expression with E6/E7 level in 40 cases of high-grade cervical lesions. Furthermore, the modulation of HPV-16 E6/E7 expression remarkably influenced cell proliferation, migration, and invasion, as well as the protein levels of E-cadherin and P-cadherin in cervical cell lines. Finally, the reduction of HPV-16 E6/E7 expression led to up-regulated expression of E-cadherin and down-regulated expression of P-cadherin in BALB/c-nu mouse model in vivo assay.
  
  
  CONCLUSIONS
  Our results unraveled the possibility that HPV-16 E6/E7 could promote cell invasive potential via regulating cadherin switching, and consequently contribute to progression and metastasis of cervical cancer.
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd No. 1, 310006, Hangzhou, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd No. 1, 310006, Hangzhou, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd No. 1, 310006, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd No. 1, 310006, Hangzhou, China. lbh8888@163.com.
authors.forename: Baohua
authors.initials: B
authors.lastname: Li
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020868:Gene Silencing; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D015820:Cadherins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Cadherin switch; Cervical cancer; Epithelial–mesenchymal transition; Human papillomavirus; Viral oncoproteins