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
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Ruxing Xi1, Shupei Pan1, Xin Chen2, Beina Hui1, Li Zhang1, Shenbo Fu1, Xiaolong Li3, Xuanwei Zhang1, Tuotuo Gong1, Jia Guo1, Xiaozhi Zhang1, Shaomin Che1
1Department of Radiotherapy, The First Hospital Affiliated of Xi’an Jiao Tong University, Xi’an, Shaan Xi, 710061, P.R.China
2Department of Radiotherapy, People’s Hospital of Shaanxi Province, Xi’an, Shaan Xi, 710068, P.R.China
3Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, Shaan Xi, 710054, P.R.China
Xiaozhi Zhang, email: firstname.lastname@example.org
Shaomin Che, email: email@example.com
Keywords: esophageal squamous cell carcinoma, HPV16 E6-E7, CSCs, PI3K, p75NTR
Received: October 22, 2015 Accepted: July 16, 2016 Published: July 30, 2016
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.
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