NANOG expression in human development and cancerogenesis

Abstract

NANOG is an important stem cell transcription factor involved in human development and cancerogenesis. Its expression is complex and regulated on different levels. Moreover, NANOG protein might regulate hundreds of target genes at the same time. NANOG is crucial for preimplantation development phase and progressively decreases during embryonic stem cells differentiation, thus regulating embryonic and fetal development. Postnatally, NANOG is undetectable or expressed in very low amounts in the majority of human tissues. NANOG re-expression can be detected during cancerogenesis, already in precancerous lesions, with increasing levels of NANOG in high grade dysplasia. NANOG is believed to enable cancer cells to obtain stem-cell like properties, which are believed to be the source of expanding growth, tumor maintenance, metastasis formation, and tumor relapse. High NANOG expression in cancer is frequently associated with advanced stage, poor differentiation, worse overall survival, and resistance to treatment, and is therefore a promising prognostic and predictive marker. We summarize the current knowledge on the role of NANOG in cancerogenesis and development, including our own experience. We provide a critical overview of NANOG as a prognostic and diagnostic factor, including problems regarding its regulation and detection. Impact statement NANOG has emerged as a key stem cell transcription factor in normal development and cancerogenesis. It is generally regarded as a good prognostic and predictive factor in various human cancers. It is less known that it is expressed already at precancerous stages in various organs, suggesting that finally an ideal candidate diagnostic marker has been discovered, enabling to distinguish between true dysplasia and reactive atypia. NANOG regulation is complex, and new insights into our understanding of its regulation might provide important information for future development in a broad field of two entirely different processes, i.e. normal development and cancerogenesis, showing how a physiologic mechanism can be used and abused, transforming itself into a key mechanism of disease development and progression.

Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma

“…Elevated NANOG expression has thus been reported in various cancer types (lung, breast, colorectal, etc. ), including in OSCC, and it is believed that it can be used as a prognostic biomarker [6][7][8][9][10].…”

“…Some NANOG regulators have been previously described as being associated with NANOG expression in head and neck SCC [ 2 , 12 , 17 – 20 ]. However, the biological implication and underlying mechanisms still remain unclear and very little is known about the association of microRNAs (miRNAs) and NANOG in OSSC [ 10 , 16 , 21 – 23 ]. Furthermore, there are limited data on NANOG expression in OSCC (i) in correlation with expression of miRNAs whose target is NANOG , (ii) in correlation with its known protein regulators, (iii) in correlation with the methylation status of its promoter, and (iv) in correlation with the copy number variation (CNV) of the NANOG gene.…”

HLF is a Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma Based on Bioinformatic Analysis and Experimental Validation

“…As well, HLF form a positive feedback loop with the pluripotency factors OCT4 and SOX2, and the feedforward system composed of OCT4 and SOX2 and NANOG also regulates the transcription of their own coding genes by forming an interconnected self regulatory network. Recent studies have shown that Sox2, Oct4 and Nanog are involved in regulating the proliferation of HNSCC cancer stem cells and promoting tumor growth [17][18][19][20][21][22][23]. Therefore, it may be hypothesised that HLF plays a major role in the development of HNSCC.…”

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma

“…NANOG is a stem cell transcription factor, involved in the development of various human cancers including OSCC. The majority of published studies have focused on protein expression and have shown promising results, suggesting that NANOG should be considered as a diagnostic and prognostic marker of oral precancerosis and OSCC ( 8 , 14 – 16 ). However, there is limited information regarding NANOG regulation by lncRNAs and miRNAs in OSCC development.…”