Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1- and TCF-dependent mechanisms

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.

Abstract

Embryonic NANOG (NANOG1) 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 NANOG1 and NANOGP8 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-cateninHigh. Moreover, single NANOG1-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 NANOG1-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 NANOG1-promoter via the octamer M1 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 NANOG1-promoter. © AlphaMed Press.

Citation

Ibrahim, E. E., Babaei-Jadidi, R., Saadeddin, A., Spencer-Dene, B., Hossaini, S., Abuzinadah, M., Li, N., Fadhil, W., Ilyas, M., Bonnet, D., & Nateri, A. S. (2012). Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1- and TCF-dependent mechanisms. STEM CELLS, 30(10), 2076-2087. https://doi.org/10.1002/stem.1182

• Journal Article Type: Article
• Online Publication Date: Sep 20, 2012
• Publication Date: Oct 1, 2012
• Deposit Date: Sep 11, 2024
• Journal: Stem Cells
• Print ISSN: 1066-5099
• Electronic ISSN: 1549-4918
• Publisher: AlphaMed Press
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 10
• Pages: 2076-2087
• DOI: https://doi.org/10.1002/stem.1182
• Keywords: NANOG1, β-Catenin, c-JUN, Cancer stem cell
• Public URL: https://nottingham-repository.worktribe.com/output/39457933
• Publisher URL: https://academic.oup.com/stmcls/article/30/10/2076/6415775?login=true