Roles Played by YY1 in Embryonic, Adult and Cancer Stem Cells

Abstract

Accumulating evidence strongly indicates that the presence of cancer stem cells (CSCs) leads to the emergence of worse clinical scenarios, such as chemo- and radiotherapy resistance, metastasis, and cancer recurrence. CSCs are a highly tumorigenic population characterized by self-renewal capacity and differentiation potential. Thus, CSCs establish a hierarchical intratumor organization that enables tumor adaptation to evade the immune response and resist anticancer therapy. YY1 functions as a transcription factor, RNA-binding protein, and 3D chromatin regulator. Thus, YY1 has multiple effects and regulates several molecular processes. Emerging evidence indicates that the development of lethal YY1-mediated cancer phenotypes is associated with the presence of or enrichment in cancer stem-like cells. Therefore, it is necessary to investigate whether and to what extent YY1 regulates the CSC phenotype. Since CSCs mirror the phenotypic behavior of stem cells, we initially describe the roles played by YY1 in embryonic and adult stem cells. Next, we scrutinize evidence supporting the contributions of YY1 in CSCs from a number of various cancer types. Finally, we identify new areas for further investigation into the YY1-CSCs axis, including the participation of YY1 in the CSC niche.

Keywords: Cancer stem cells; Differentiation potential; Self‐renewal; YY1.

Fig. 1

Molecular pathways modulated by YY1 in CSCs. Molecular pathways altered by YY1 in CSCs from endometrial, brain, liver, skin, and breast cancers are shown. RER, rough endoplasmic reticulum; EMT, epithelial-mesenchymal transition

Fig. 2

Potential role of YY1 in the regulation of the CSC niche. a The use of well-known genetically engineered mouse models for cancer research with conditional ablation of YY1 in specific TACs, such as mesenchymal stem cells (MSCs), immune cells, tumor-associated fibroblasts, and adipocytes, may enable to determine the role of YY1 in tumor-associated cells (TACs) regulating the CSC niche. b YY1 is currently conceptualized as a 3D chromatin regulator; thus, it will be of interest to determine whether YY1 imposes specific gene expression in TACs supporting the CSC niche by modulating their chromatin configuration