Akt‑mediated phosphorylation of Oct4 is associated with the proliferation of stem‑like cancer cells

Oncol Rep. 2015 Apr;33(4):1621-9. doi: 10.3892/or.2015.3752. Epub 2015 Jan 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / pharmacology
  • Brain Neoplasms / chemistry
  • Carcinoma, Hepatocellular / chemistry
  • Cell Division
  • Cell Line, Tumor
  • Cell Nucleus / chemistry
  • Culture Media
  • Glioblastoma / chemistry
  • Glioblastoma / pathology*
  • Heterografts
  • Humans
  • Indoles / pharmacology
  • Liver Neoplasms / chemistry
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology*
  • Neoplastic Stem Cells / cytology*
  • Octamer Transcription Factor-3 / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / physiology*
  • Quinoxalines / pharmacology
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Receptors, Aryl Hydrocarbon / agonists
  • Signal Transduction
  • Spheroids, Cellular
  • Thiazoles / pharmacology

Substances

  • 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • Akt-I-1,2 compound
  • Benzylamines
  • Culture Media
  • Indoles
  • Neoplasm Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Quinoxalines
  • RNA, Small Interfering
  • Receptors, Aryl Hydrocarbon
  • Thiazoles
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt