Abstract
Recent discoveries have indicated that tumorigenesis arises from a population of cells with self-renewability and pluripotency characteristics. These led to the theory of cancer stem cells, in which these cells carry molecular signatures similar to embryonic stem cells. Homeobox protein NANOG is a transcription factor that helps embryonic stem cells maintain pluripotency. It has been identified to be highly expressed in several types of tumors. Further studies have shown the linkage of NANOG overexpression to malignancy and therapeutic resistance, however very limited research has clearly identified NANOG role in malignancy and therapeutic response of glioma. NANOG expression is regulated by p53, a cancer suppressor, which when lost, led to NANOG overexpression. The latter overexpression in glioma led to increase in its growth. NANOG was also found to be regulator of focal adhesion kinase (FAK), a matricellular protein responsible for motility of tumor cells in metastases. NANOG overexpression is indirectly induced by the use of temozolomide through c-MET activation. Despite its therapeutic resistance effect, resveratrol is a promising therapy for limiting NANOG expression. The findings in the present review argues for NANOG utilization as a therapeutic target for glioma.
Keywords
transcription factor, NANOG, p53, glioma, cancer stem cells, malignancy biomarker, resveratrol
References
Walters DK, Steinmann P, Langsam B, Schmutz S, Born W, Fuchs B. Identification of potential chemoresist-ance genes in osteosarcoma. Anticancer Res 2008; 7. PMID: 18507006
Poon MW, Zhuang JTF, Wong STS, Sun S, Zhang XQ, Leung GKK. Co-expression of cytoskeletal protein ad-ducin 3 and CD133 in neurospheres and a temozolomide-resistant subclone of glioblastoma. Anticancer Res 2015;
PMID: 26637861
Jun HJ, Bronson RT, Charest A. Inhibition of EGFR induces a c-MET-driven stem cell population in glioblas-toma: MET is required for stemness in glioblastoma. Stem Cells 2014; 32(2): 338–348. DOI: 10.1002/stem.1554
Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Su-zuki K, et al. Resveratrol promotes proteasome-dependent degradation of NANOG via p53 activation and induces differentiation of glioma stem cells. Stem Cell Res 2013; 11(1): 601–610. DOI: 10.1016/j.scr.2013.04.004