Phosphorylation of oct4 serine 236 inhibits germ cell tumor growth by inducing differentiation

Dong Keon Kim, Bomin Song, Suji Han, Hansol Jang, Seung Hyun Bae, Hee Yeon Kim, Seon Hyeong Lee, Seungjin Lee, Jong Kwang Kim, Han Seong Kim, Kyeong Man Hong, Byung Il Lee, Hong Duk Youn, Soo Youl Kim, Sang Won Kang, Hyonchol Jang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Octamer-binding transcription factor 4 (Oct4) plays an important role in maintaining pluripotency in embryonic stem cells and is closely related to the malignancies of various cancers. Although posttranslational modifications of Oct4 have been widely studied, most of these have not yet been fully characterized, especially in cancer. In this study, we investigated the role of phosphorylation of serine 236 of OCT4 [OCT4 (S236)] in human germ cell tumors (GCTs). OCT4 was phosphorylated at S236 in a cell cycle-dependent manner in a patient sample and GCT cell lines. The substitution of endogenous OCT4 by a mimic of phosphorylated OCT4 with a serine-to-aspartate mutation at S236 (S236D) resulted in tumor cell differentiation, growth retardation, and inhibition of tumor sphere formation. GCT cells expressing OCT4 S236D instead of endogenous OCT4 were similar to cells with OCT4 depletion at the mRNA transcript level as well as in the phenotype. OCT4 S236D also induced tumor cell differentiation and growth retardation in mouse xenograft experiments. Inhibition of protein phosphatase 1 by chemicals or short hairpin RNAs increased phosphorylation at OCT4 (S236) and resulted in the differentiation of GCTs. These results reveal the role of OCT4 (S236) phosphorylation in GCTs and suggest a new strategy for suppressing OCT4 in cancer.

Original languageEnglish
Article number2601
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume12
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Cancer differentiation
  • Germ cell tumor
  • Oct4
  • OCT4 inhibitor
  • OCT4 serine 236
  • Phosphorylation

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