Identification of DPPA4 and DPPA2 as a novel family of pluripotency-related oncogenes

Po Yuan Tung, Natalia V. Varlakhanova, Paul S Knoepfler

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

In order to identify novel pluripotency-related oncogenes, an expression screen for oncogenic foci-inducing genes within a retroviral human embryonic stem cell cDNA library was conducted. From this screen, we identified not only known oncogenes but also intriguingly the key pluripo-tency factor, DPPA4 (developmental pluripotency-associated four) that encodes a DNA binding SAP domain-containing protein. DPPA4 has not been previously identified as an oncogene but is highly expressed in embryonal carcinomas, pluripotent germ cell tumors, and other cancers. DPPA4 is also mutated in some cancers. In direct transformation assays, we validated that DPPA4 is an onco-gene in both mouse 3T3 cells and immortalized human dermal fibroblasts. Overexpression of DPPA4 generates oncogenic foci (sarcoma cells) and causes anchorage-independent growth. The in vitro transformed cells also give rise to tumors in immunodeficient mice. Furthermore, functional analyses indicate that both the DNA-binding SAP domain and the histone-binding C-terminal domain are critical for the oncogenic transformation activity of DPPA4. Downregulation of DPPA4 in E14 mouse embryonic stem cells and P19 mouse embryonic carcinoma cells causes decreased cell proliferation in each case. In addition, DPPA4 overexpression induces cell proliferation through genes related to regulation of G1/S transition. Interestingly, we observed similar findings for family member DPPA2. Thus, we have identified a new family of pluripotency-related oncogenes consisting of DPPA2 and DPPA4. Our findings have important implications for stem cell biology and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2330-2342
Number of pages13
JournalStem Cells
Volume31
Issue number11
DOIs
StatePublished - 2013

Keywords

  • Cancer
  • Cancer stem cells
  • Cell cycle
  • DPPA2
  • DPPA4
  • Embryonic stem cells
  • Pluripotency-related oncogenes
  • Pluripotent stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Fingerprint Dive into the research topics of 'Identification of DPPA4 and DPPA2 as a novel family of pluripotency-related oncogenes'. Together they form a unique fingerprint.

  • Cite this