title: Akt‑mediated phosphorylation of Oct4 is associated with the proliferation of stem‑like cancer cells.
abstract: Oct4 protein encoded by POU5F1 plays a pivotal role in maintaining the self‑renewal of pluripotent stem cells; however, its presence in cancer cells remains controversial. In the present study, we provided evidence that the transcripts of authentic OCT4 gene (OCT4A) and its multiple pseudogenes were detected in a variety of cancer cell lines. A few major bands were also detected by western blotting using an anti‑Oct4A monoclonal antibody. Moreover, an anti‑Oct4‑pT235 antibody was used to identify a band in the majority of the tested cancer cell lines that coincided with one of the anti‑Oct4A bands which was decreasable by a specific shRNA. The Oct4‑pT235 signals were also detected in human glioblastoma and liver cancer specimens by immunofluorescence microscopy and immunohistochemistry. U87 glioblastoma cells were cultured in a neural stem cell medium to induce the formation of neurospheres rich in stem‑like cancer cells. The levels of Oct4‑pT235 in the sphere cells were markedly increased compared to their monolayer parental cells, a result that was accompanied by upregulation of the PI3K‑Akt pathway. Akti‑1/2, a specific inhibitor of Akt, effectively reduced the level of Oct4‑pT235 and attenuated the proliferation of U87 sphere cells. ITE, an agonist of the aryl hydrocarbon receptor, also significantly attenuated the Akt‑mediated phosphorylation of Oct4 in glioblastoma and liver cancer cells, and reduced their tumorigenic potential in a xenograft tumor model. Taken together, we concluded that the Akt‑mediated phosphorylation of Oct4A or its homolog protein was associated with the proliferation of stem‑like cancer cells that may serve as a novel biomarker and drug target for certain types of cancer.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Li
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Yin
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tong
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: He
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Hang-Ping
authors.initials: HP
authors.lastname: Yao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001932:Brain Neoplasms / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000737:chemistry; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D003470:Culture Media; D005909:Glioblastoma / Q000737:chemistry / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008113:Liver Neoplasms / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C548651:2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester; C501521:Akt-I-1,2 compound; D001596:Benzylamines; D003470:Culture Media; D007211:Indoles; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011810:Quinoxalines; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D013844:Thiazoles; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt