Open AccessEmbryonic NANOG Activity Defines Colorectal Cancer Stem Cells and Modulates through AP1‐ and TCF‐dependent Mechanisms
Author(s) -
Ibrahim Elsayed E.,
BabaeiJadidi Roya,
Saadeddin Anas,
SpencerDene Bradley,
Hossaini Sina,
Abuzinadah Mohammed,
Li Ningning,
Fadhil Wakkas,
Ilyas Mohammad,
Bonnet Dominique,
Nateri Abdolrahman S.
Publication year - 2012
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.1182
Subject(s) - homeobox protein nanog , biology , embryonic stem cell , stem cell , sox2 , cancer stem cell , wnt signaling pathway , cancer research , clonogenic assay , microbiology and biotechnology , carcinogenesis , rex1 , embryoid body , induced pluripotent stem cell , cancer , genetics , cell culture , gene , signal transduction
Abstract Embryonic NANOG ( NANOG 1) is considered as an important regulator of pluripotency while NANOGP8 (NANOG‐pseudogene) plays a role in tumorigenesis. Herein, we show NANOG is expressed from both NANOG 1 and NANOGP 8 in human colorectal cancers (CRC). Enforced NANOG1‐expression increases clonogenic potential and tumor formation in xenograft models, although it is expressed only in a small subpopulation of tumor cells and is colocalized with endogenous nuclear β‐catenin High . Moreover, single NANOG 1‐CRCs form spherical aggregates, similar to the embryoid body of embryonic stem cells (ESCs), and express higher levels of stem‐like Wnt‐associated target genes. Furthermore, we show that NANOG 1‐expression is positively regulated by c‐JUN and β‐catenin/TCF4. Ectopic expression of c‐Jun in murine Apc Min/+ ‐ESCs results in the development of larger xenograft tumors with higher cell density compared to controls. Chromatin immunoprecipitation assays demonstrate that c‐JUN binds to the NANOG 1‐promoter via the octamer M 1 DNA element. Collectively, our data suggest that β‐Catenin/TCF4 and c‐JUN together drive a subpopulation of CRC tumor cells that adopt a stem‐like phenotype via the NANOG 1‐promoter. S TEM C ells 2012;30:2076–2087