Embryonic NANOG Activity Defines Colorectal Cancer Stem Cells and Modulates through AP1‐ and TCF‐dependent Mechanisms123. (20th September 2012)

• Record Type: Journal Article
• Authors: Ibrahim, Elsayed E.; Babaei‐Jadidi, Roya; Saadeddin, Anas; Spencer‐Dene, Bradley; Hossaini, Sina; Abuzinadah, Mohammed; Li, Ningning; Fadhil, Wakkas; Ilyas, Mohammad; Bonnet, Dominique; Nateri, Abdolrahman S.
• Is Part Of: Stem cells. Volume 30:Number 10(2012)
• Page Start: 2076
• Page End: 2087
• Publication Date: 2012-09-20
• Subjects: NANOG1 -- β‐Catenin -- c‐JUN -- Cancer stem cell; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1182
• Languages: English
• ISSNs: 1066-5099

Abstract

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. STEM Cells 2012;30:2076–2087