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

Gustavo Ulises Martinez-Ruiz,Abigail Morales-Sanchez,Angel Francisco Pacheco-Hernandez

doi:10.1007/s12015-021-10151-9

Gustavo Ulises Martinez-Ruiz, Abigail Morales-Sanchez + Show 1 more

Open Access

https://doi.org/10.1007/s12015-021-10151-9

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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.Graphical

Highlights

Yin yang-1 (YY1) has been identified as a transcription factor with a dual function activating or repressing gene expression
cancer stem cells (CSCs) mirror the stemness properties of self-renewal and differentiation potential; we describe the role of YY1 in the biology of embryonic and adult stem cell (SC) as a biological framework to show the role of YY1 in CSCs in various cancer types
Since YY1 mediates specific 3D chromatin configurations needed for cell identity, we suggest that YY1 may govern both CSCs and the CSC niche by imposing cell type-specific chromatin configurations

Summary

Introduction

Yin yang-1 (YY1) has been identified as a transcription factor with a dual function activating or repressing gene expression. The transcription factors Oct, Sox, and Nanog mediate the core gene expression module by forming specialized autoregulatory and feedforward loops via interactions with their own and target promoter sequences [44, 45]. YY1 is apparently associated with the three modules of stemness regulation in ESCs. YY1 mediates transcriptional activation of the Oct and Sox genes by forming long-range interactions by looping [46]. The role of YY1 in stem cells associated with the brain and epidermal development from the ectoderm germ cell lineages was investigated using conditional KO mice (Table 1). Another study demonstrated that knockout of the YY1 gene during cortex development decreased the forebrain size due to reduced proliferation and increased apoptotic death in cortical progenitor cells [52]. Studies using all these mouse models demonstrated that YY1 modulates brain development by regulating the proliferation, cell death, mitochondrial metabolism, and 3D chromatin configuration. Analysis of the organs and tissues generated from this layer demonstrated the

Hearth Skeletal muscle

Endoderm Intestine

Findings

Concluding Remarks