Colorectal carcinoma (CRC) is the second highest cancer-specific mortality in the U.S. population. There remains a need to develop effect therapeutics to prevent and/or treat CRC.
Nanog was identified to be a core embryonic stem cell gene (Chambers et al., 2003, Cell 113:643-55), and was later determined to be associated with a family of eleven pseudogenes on chromosome 12 with the original parent gene (Booth et al., 2004, Genomics 84:229-38). Other members of the family may influence Nanog's function in carcinoma cells, for example by reactivation.
The cancer stem cell hypothesis postulates that a small pluripotent population of cancer cells generates cancer heterogeneity and resistance to chemotherapy and radiation therapy. Three transcription factors, SOX2, OCT4 and Nanog form a core regulatory network that coordinately determines embryonic stem cell self-renewal and differentiation (Zhang et al., 2006, FEBS J 273:1723-30). Cultured cancer cells, as well as xenograft and human primary prostate cancer cells express a functional variant of Nanog, NanogP8, which is enriched in putative cancer stem/progenitor cell populations (Zhang et al.; and Jeter et al. 2009, Stem Cells 27:993-1005). Nanog protein expression is functionally important for tumor development based because knockdown of Nanog expression inhibits growth of xenografts of cancer cells from cancer cell lines Du145 HPCa and LAPC4 (prostate), MCF7 (breast cancer), and Colo320 (colon cancer) (Jeter et al.). NanogP8 is also expressed in human glioblastoma cells (Zbinden et al. 2010, EMBO J 29:2659-74).
The role of Nanog and its pseudogenes in tumorigenesis and progression of metastasis for a number of cancers, including gastric, colorectal (CRC), breast, glioblastoma, cervical cancers is currently unknown.