title: The virus-induced protein APOBEC3G inhibits anoikis by activation of Akt kinase in pancreatic cancer cells.
abstract: Pancreatic cancer is one of the more common cancers with a poor prognosis. Some varieties of cancer are related to virus infection. As a virus-induced protein, APOBEC3G (A3G) presents extensive anti-virus ability, but the role of A3G in pancreatic cancer was previously unknown. The expression of A3G in pancreatic cancer was examined using TaqMan real-time qPCR, immunohistochemical and immunofluorescent staining. Subsequently, the role of A3G in pancreatic cancer was evaluated in vivo using the tumor xenograft model. Anoikis was detected by colony formation assay and flow cytometry in vitro. The Akt kinase activity and target protein PTEN were examined by co-immunoprecipitation and immunoblot. The virus-induced protein A3G was significantly up-regulated in pancreatic cancer, and the up-regulation of A3G promoted xenograft tumor formation. A3G inactivated PTEN by binding to the C2 tensin-type and PDZ domains, thereby inducing anoikis resistance through Akt activation. Our results demonstrate that the up-regulation of A3G in pancreatic cancer cells induces anoikis resistance, and they provide novel insight into the mechanism by which A3G affects the malignant behavior of pancreatic cancer cells.
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Tian-Hui
authors.initials: TH
authors.lastname: Pan
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: 1] Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China [2] Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Li-Tao
authors.initials: LT
authors.lastname: Jia
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Zhu
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Jian-Shan
authors.initials: JS
authors.lastname: Mao
authors.affiliation: 1] Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China [2] Cancer Institute and Education Ministry Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhu
authors.affiliation: Laboratory of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Cai
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D023102:Anoikis / Q000502:physiology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase