Open AccessFunctional Evidence that the Self‐Renewal Gene NANOG Regulates Human Tumor Development
Author(s) -
Jeter Collene R.,
Badeaux Mark,
Choy Grace,
Chandra Dhyan,
Patrawala Lubna,
Liu Can,
CalhounDavis Tammy,
Zaehres Holm,
Daley George Q.,
Tang Dean G.
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.29
Subject(s) - homeobox protein nanog , biology , rex1 , nanog homeobox protein , cancer stem cell , embryonic stem cell , stem cell , clonogenic assay , cancer cell , gene knockdown , cancer research , microbiology and biotechnology , cellular differentiation , cancer , cell , induced pluripotent stem cell , genetics , cell culture , gene
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. S tem C ells 2009;27:993–1005