Functional evidence that the self-renewal gene NANOG regulates human tumor development

Stem Cells. 2009 May;27(5):993-1005. doi: 10.1002/stem.29.


Tumor development has long been known to resemble abnormal embryogenesis. The embryonic stem cell (ESC) self-renewal gene NANOG is purportedly expressed by some epithelial cancer cells but a causal role in tumor development has remained unclear. Here, we provide compelling evidence that cultured cancer cells, as well as xenograft- and human primary prostate cancer cells express a functional variant of NANOG. NANOG mRNA in cancer cells is derived predominantly from a retrogene locus termed NANOGP8. NANOG protein is detectable in the nucleus of cancer cells and is expressed higher in patient prostate tumors than matched benign tissues. NANOGP8 mRNA and/or NANOG protein levels are enriched in putative cancer stem/progenitor cell populations. Importantly, extensive loss-of-function analysis reveals that RNA interference-mediated NANOG knockdown inhibits tumor development, establishing a functional significance for NANOG expression in cancer cells. Nanog short hairpin RNA transduced cancer cells exhibit decreased long-term clonal and clonogenic growth, reduced proliferation and, in some cases, altered differentiation. Thus, our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Clone Cells
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Male
  • Nanog Homeobox Protein
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Pseudogenes
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Transcription, Genetic
  • Transduction, Genetic


  • Homeodomain Proteins
  • Hyaluronan Receptors
  • NANOG protein, human
  • Nanog Homeobox Protein
  • RNA, Messenger
  • RNA, Small Interfering