Targeting cancer stem cells: emerging role of Nanog transcription factor

Abstract

The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the therapeutic efficacy of targeting Nanog as a cancer treatment method, current animal experiments using siNanog or shNanog have shown the promising therapeutic potential of Nanog targeting in several types of cancer.

Suppressive Effect of Crocin and Cisplatin on Pluripotency Genes Expression in Human Cervical Cancer Cells

“…Sox2 and Nanog are transcription factors that are essential for maintaining self-renewal or pluripotency of undifferentiated embryonic stem cells (17). Up-regulation of these factors and disregulation of downstream regulatory pathways affects several aspects of cancer development such as cell proliferation, self-renewal, motility, epithelialmesenchymal transition, and drug-resistance (18). The effects of Cisplatin as a chemotherapy drug on pluripotency genes have been evaluated before (19,20).…”

New Opportunities and Challenges to Defeat Cancer Stem Cells

“…NANOG is a homeodomain-containing transcription factor that is part of the key set of transcription factors involved in the maintenance of pluripotency and self-renewal in undifferentiated embryonic stem cells [118]. In CSCs of various cancers, NANOG expression levels are higher including breast, cervix, oral, kidney, prostate, lung, gastric, brain, pancreas, and ovarian cancer [47, 119-125].…”

“…In CSCs of various cancers, NANOG expression levels are higher including breast, cervix, oral, kidney, prostate, lung, gastric, brain, pancreas, and ovarian cancer [47, 119-125]. Increased expression of NANOG is shown as an indicator of a poor prognosis for ovarian, colorectal, and breast cancer patients [118]. In oral squamous cell and lung adenocarcinoma, higher expression of NANOG was associated with advanced cancer stage and shorter patient survival rate.…”

“…In oral squamous cell and lung adenocarcinoma, higher expression of NANOG was associated with advanced cancer stage and shorter patient survival rate. NANOG expression has also been shown to be higher in CSCs than in other cancer cells in several types of cancers [118]. CD133 + cancer cells express significantly higher levels of NANOG in comparison to CD133 − cancer cells.…”

“…Functional studies have shown that NANOG is not only a marker for CSCs, but also promotes CSC characteristics across multiple cancers. Overexpression of NANOG in cancer cells has been linked to increased proliferation rate in vitro and tumor growth in vivo [118]. …”