title: Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation,             migration and invasion in vitro and accelerates tumor growth in vivo.
abstract: High-risk human papillomaviruses (HR-HPVs) are consistently associated with             human cervical cancer Additionally, the early oncoproteins of HPVs E5, E6 and             E7 are known to contribute to tumor progression. The role of E5 is still nebulous.             In this study, we aimed to explore the mechanism of E5 action during the human             cervical carcinogenesis process. We created four cell models overexpressing HPV16             or HPV18 E5 (HPV16/18 E5) and investigated their ability to proliferate, along             with their metastatic characteristics such as migration and invasion. The expression             of HPV16/18 E5 protein in various cell lines was analyzed by reverse transcriptase-polymerase             chain reaction (RT-PCR). In addition, we compared the levels of phosphorylated             paxillin as well as E-cadherin in cell models and controls by western blot analysis.             Finally, we assessed the tumor growth rate of human cervical cancer cells overexpressing             HPV16/18 E5 in vivo. We discovered that the expression of HPV16/18 E5 consistently             increased the malignant potential of various human cervical cancer cells compared             with the primary counterparts. We demonstrated the involvement of HPV16/18 E5             in proliferation, migration, invasion and regulation of the actin cytoskeleton             in human cervical cancer cells. In particular we discovered that HPV16/18 E5 overexpression             in human cervical cancer cells correlated with higher levels of paxillin proteins             phosphorylated on tyrosine residues and with the downregulation of E-cadherin.             Importantly, injection of HPV16/18 E5-overexpressing human cervical cancer cells             into mice increased both HPV-and non-HPV-derived tumor growth. Collectively, our             data indicate that HPV16/18 E5 influences progression of the human cervical cancer             malignant phenotype. This study provides new insights into HPV16/18 E5 as a possible             agent that may have an impact on the therapeutic strategies targeting human cervical             cancer.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Liao
authors.forename: Dongrui
authors.initials: D
authors.lastname: Deng
authors.forename: Weina
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yunping
authors.initials: Y
authors.lastname: Lu
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D052162:Human papillomavirus 16 / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing; D000086082:Viroporin Proteins
chemical_list: D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins