title: HPV16 E6-E7 induces cancer stem-like cells phenotypes in esophageal squamous cell carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in vivo.
abstract: High-risk human papillomavirus (HPV), especially HPV16, correlates with cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have reported that HPV16 related with a poor prognosis of ESCC patients in China. We aim to investigate the potential role and mechanism of HPV16 in ESCC development and progress. Our following researches demonstrated that ESCC cells which were stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer stem-like cells (CSCs) phenotype, such as: migration, invasion, spherogenesis, high expression of CSCs marker in ESCC---p75NTR, chemoresistance, radioresistance, anti-apoptosis ability in vitro and cancerogenesis in vivo. HPV16 E6-E7 induced PI3K/Akt signaling pathway activation and this affect could be effectively inhibited by LY294002, a specific PI3K inhibitor. It was also indicated that the inhibition of PI3K/Akt signaling pathway by PI3K and Akt siRNA reverse the effect which induced by HPV16 E6-E7 in ESCC cells. Taken together, the present study demonstrates that HPV16 E6-E7 promotes CSCs phenotype in ESCC cells through the activation of PI3K/Akt signaling pathway. Targeting the PI3K/Akt signaling pathway in HPV16 positive tissues is an available therapeutic for ESCC patients.
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Ruxing
authors.initials: R
authors.lastname: Xi
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Shupei
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Radiotherapy, People's Hospital of Shaanxi Province, Xi'an, Shaan Xi, 710068, P.R.China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Beina
authors.initials: B
authors.lastname: Hui
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Shenbo
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Radiotherapy, The People's Liberation Army 323 Hospital, Xi'an, Shaan Xi, 710054, P.R.China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Xuanwei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Tuotuo
authors.initials: T
authors.lastname: Gong
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Hospital Affiliated of Xi'an Jiao Tong University, Xi'an, Shaan Xi, 710061, P.R.China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Che
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D002453:Cell Cycle; D002465:Cell Movement; D002470:Cell Survival; D002867:Chromones / Q000737:chemistry; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000821:virology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009025:Morpholines / Q000737:chemistry; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002867:Chromones; C068651:E6 protein, Human papillomavirus type 16; D009025:Morpholines; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D017475:Receptors, Nerve Growth Factor; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: CSCs; HPV16 E6-E7; PI3K; esophageal squamous cell carcinoma; p75NTR