Aktmediated phosphorylation of Oct4 is associated with the proliferation of stemlike cancer cells

Author：

E-ISSN： 1791-2431|33|4|1621-1629

ISSN： 1021-335X

Source： Oncology Reports, Vol.33, Iss.4, 2015-01, pp. : 1621-1629

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Abstract

Oct4 protein encoded by POU5F1 plays a pivotal role in maintaining the selfrenewal 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 antiOct4A monoclonal antibody. Moreover, an antiOct4pT235 antibody was used to identify a band in the majority of the tested cancer cell lines that coincided with one of the antiOct4A bands which was decreasable by a specific shRNA. The Oct4pT235 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 stemlike cancer cells. The levels of Oct4pT235 in the sphere cells were markedly increased compared to their monolayer parental cells, a result that was accompanied by upregulation of the PI3KAkt pathway. Akti1/2, a specific inhibitor of Akt, effectively reduced the level of Oct4pT235 and attenuated the proliferation of U87 sphere cells. ITE, an agonist of the aryl hydrocarbon receptor, also significantly attenuated the Aktmediated 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 Aktmediated phosphorylation of Oct4A or its homolog protein was associated with the proliferation of stemlike cancer cells that may serve as a novel biomarker and drug target for certain types of cancer.