Pluripotency transcription factors and cancer stem cells: small genes make a big difference

Abstract

Cancer stem cells (CSCs) are thought to drive uncontrolled tumor growth, and the existence of CSCs has recently been proven by direct experimental evidence, including tracing cell lineages within a growing tumor. However, CSCs must be analyzed in additional cancer types. Cancer stem cell-like cells (CSCLCs) are a good alternative system for the study of CSCs, which hold great promise for clinical applications. OCT4, NANOG, and SOX2 are three basic transcription factors that are expressed in both CSCLCs and embryonic stem cells (ESCs). These transcription factors play critical roles in maintaining the pluripotence and self-renewal characteristics of CSCLCs and ESCs. In this review, we discuss the aberrant expression, isoforms, and pseudogenes of OCT4, NANOG, and SOX2 in the CSCLC niche, which contribute to the major differences between CSCLCs and ESCs. We also highlight an anticancer therapy that involves killing specific cancer cells directly by repressing the expression of OCT4, NANOG, or SOX2. Importantly, OCT4, NANOG, and SOX2 provide great promise for clinical applications because reducing their expression or blocking the pathways in which they function may inhibit tumor growth and turn-off the cancer “switch.” In the future, a clear understanding of transcription factor regulation will be essential for elucidating the roles of OCT4, NANOG, and SOX2 in tumorigenesis, as well as exploring their use for diagnostic and therapeutic purposes.

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

“…They play critical roles in maintaining the pluripotency and self-renewal (stemness) characteristics of human embryonic stem cells (ESCs) (5) and contribute to the reprogramming of adult somatic cells into an ESC-like state (4). Their gene expression has been reported in cancer stem cell niche and tumor cells in higher levels than in nontumor tissues (1).…”

Cancer stem cells in human digestive tract malignancies

“…CSCs, similar to embryonal carcinoma cells (ECCs) [14], are able to reproduce the same morphological and antigenic patterns as the original tumor, and this characteristic maintains upon serial transplantation of tumor cells into secondary and tertiary recipients. & Elevated expression of major stemness transcriptional factors (TFs) including OCT4, SOX2, and NANOG, and also genes associated with tumorigenesis and immortality of cells such as BMI1 and TERT [15][16][17]. & Resistance to ionizing radiation and cytotoxic chemotherapy by overexpression of DNA repair enzymes and drug efflux pumps, such as ABCG2/BCRP1, ABCB1/MDR1, MRP1, and MRP2, as well as alterations in cell cycle check point control and apoptotic pathways [18,19].…”

The Expressions of Cancer Stem Cell Markers and Nonclassical HLA antigens in Breast Tumors

“…Similar to embryonic stem cells (ESCs), CSCs have self-renewal, undifferentiated, and pluripotency properties (7,36,37). Human Nanog is one of the crucial transcription factors that is strongly related with self-renewal and maintaining the undifferentiated state of ESCs (38).…”