The transcription factor NANOG regulates self-renewal and pluripotency in embryonic cells, and its downregulation leads to cell differentiation. Recent studies have linked upregulation of NANOG in various cancers and the regulation of expression of different molecules, and vice versa, to induce proliferation, metastasis, invasion and chemoresistance. Thus NANOG is an oncogene that functions by inducing stem cells' circuitries and heterogeneity in cancers. Understanding NANOG's role in various cancers may lead to it becoming a therapeutic target to halt cancer progression. The NANOG network can also be targeted to resensitize resistant cancer cells to conventional therapies. The current review focuses on NANOG regulation in the various signaling networks leading to cancer progression and chemoresistance, and highlights the therapeutic aspect of targeting NANOG in various cancers.
Keywords: NANOG; cancer; cancer stem cells; epigenetic modification; mutations; reprogramming.
Lay abstract NANOG is a gene that is mainly expressed during development of the embryo. In adult tissues, NANOG is hardly expressed. In embryonal cells, NANOG is responsible for generating stem cells. Once the cells are differentiated into their specific function, they no longer need this renewing property. So expression of NANOG in differentiated ‘adult’ cells is harmful as it helps tumor cells to grow. NANOG expression also enables the tumor cells to keep on evolving their microenvironment, thus making it difficult for conventional therapy to destroy them. This review highlights the factors that influence NANOG’s expression in cancer progression and chemoresistance and how it can be targeted for therapy.