Begell House Inc.
Critical Reviews™ in Oncogenesis
CRO
0893-9675
16
3-4
2011
Preface: Special Issue on Yin Yang 1 and Oncogenesis
141-142
10.1615/CritRevOncog.v16.i3-4.10
Benjamin
Bonavida
Department of Microbiology, Immunology, &
Molecular Genetics, David Geffen School of Medicine at UCLA, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA
Mechanisms of Yin Yang 1 in Oncogenesis: The Importance of Indirect Effects
143-161
10.1615/CritRevOncog.v16.i3-4.20
Michael L.
Atchison
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, USA
Arindam
Basu
University of Pennsylvania, School of Veterinary Medicine, Department of Animal Biology, Philadelphia, Pennsylvania, USA
Kristina
Zaprazna
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Madhusudhan
Papasani
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
transcription
Polycomb
DNA repair
mutagenesis
genome stability
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that performs numerous functions including transcriptional regulation, cell growth control, apoptosis, large-scale chromosomal dynamics, and X-chromosome inactivation. YY1 clearly is able to control cell functions, including proliferation, by acting as a transcription factor either to activate or repress specific genes. Based on its ability to regulate cell growth control genes, it has been argued that YY1 can function as an oncogene that initiates oncogenesis. Although this is an attractive hypothesis, no reports indicate that YY1 can acutely transform cells in culture or form tumors within animals when overexpressed. Thus, it remains unclear whether YY1 is a "classic" oncogene. However, YY1 controls many diverse cell functions, and these functions may provide clues to its role in oncogenesis. We propose that in many cases YY1 may function in oncogenesis and disease progression through "indirect" effects by virtue of its role in either recruiting Polycomb group proteins to DNA, regulating mutator protein accumulation, controlling large-scale chromosomal dynamics or genomic integrity. Disruption of these functions may causally initiate cancer or may contribute to disease progression. Targeting YY1 functions provides possible avenues for clinical intervention.
The Oncogenic Role of Yin Yang 1
163-197
10.1615/CritRevOncog.v16.i3-4.30
Qiang
Zhang
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Daniel B.
Stovall
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Kazushi
Inoue
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Guangchao
Sui
College of Life Science, Northeast Forestry University, Harbin, China; Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Yin Yang 1
transcription factor
protein modification
oncogene
tumorigenesis
Yin Yang 1 (YY1) is a transcription factor with diverse and complex biological functions. YY1 either activates or represses gene transcription, depending on the stimuli received by the cells and its association with other cellular factors. Since its discovery, a biological role for YY1 in tumor development and progression has been suggested because of its regulatory activities toward multiple cancer-related proteins and signaling pathways and its overexpression in most cancers. In this review, we primarily focus on YY1 studies in cancer research, including the regulation of YY1 as a transcription factor, its activities independent of its DNA binding ability, the functions of its associated proteins, and mechanisms regulating YY1 expression and activities. We also discuss the correlation of YY1 expression with clinical outcomes of cancer patients and its target potential in cancer therapy. Although there is not a complete consensus about the role of YY1 in cancers based on its activities of regulating oncogene and tumor suppressor expression, most of the currently available evidence supports a proliferative or oncogenic role of YY1 in tumorigenesis.
Oncogenic Potential of Yin Yang 1 Mediated Through Control of Imprinted Genes
199-209
10.1615/CritRevOncog.v16.i3-4.40
Michelle M.
Thiaville
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana
Joomyeong
Kim
Department of Biological Sciences, Louisiana State University, USA
YY1
imprinting
cancer
imprinting control region
paternally expressed gene three
guanine nucleotide binding protein
alpha stimulating
The transcription factor Yin Yang (YY) 1 is one of the most evolutionarily well-conserved DNA binding proteins that is ubiquitously expressed among different tissue types. YY1 functions as a critical regulator for a diverse set of genes, making its role in the cancerous environment elusive. Recent studies have demonstrated that clusters of YY1 binding sites are overrepresented in imprinted gene loci. These clustered binding sites may function as a molecular rheostat with respect to YY1 protein levels. YY1 levels were documented to be altered in various tumor tissues in conjunction with the transcriptional levels of the imprinted genes it regulates. This review highlights the unexplored mechanism through which fluctuations in YY1 protein levels alter the transcriptional status of imprinted genes containing clustered YY1 binding sites, which potentially could affect cancer development and/or progression.
The Novel Role of Yin Yang 1 in the Regulation of Epithelial to Mesenchymal Transition in Cancer Via the Dysregulated NF-κB/Snail/YY1/RKIP/PTEN Circuitry
211-226
10.1615/CritRevOncog.v16.i3-4.50
Benjamin
Bonavida
Department of Microbiology, Immunology, &
Molecular Genetics, David Geffen School of Medicine at UCLA, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA
Stavroula
Baritaki
Center for Systems Biomedicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
E-cadherin; epithelial-mesenchymal transition; phosphatase and tensin nuclear factor; Raf kinase inhibitor protein; Snail; Yin Yang 1
The majority of cancers develop genetic and molecular strategies to resist conventional cytotoxic therapies as well as escape from the host’s immune surveillance. These events lead to tumor persistence and spread through activation of the epithelial to mesenchymal transition (EMT) program and metastasis. Expression profiling analysis has revealed various tumor metastasis-inducing and metastasis-suppressing genes that regulate the metastatic process and maintain the microenvironment of the tumor cells. EMT in cancer entails the molecular reprogramming and phenotypic changes that characterize the conversion of immobile cancer epithelial cells to motile mesenchymal cells. A hallmark of EMT is the loss of E-cadherin, the epithelial homotypic adhesion molecule, and gain of mesenchymal markers such as vimentin and fibronectin. The molecular mechanisms underlying the initiation of EMT consist, in part, in the constitutive activation of survival signaling pathways such as the nuclear factor (NF)-κB pathway. The NF-κB pathway has been implicated directly in the regulation of EMT and indirectly through the transcription and expression of several gene products that participate in the EMT cascade, such as Snail, the metastasis-inducer and E-cadherin suppressor transcription factor. In turn, Snail represses the metastasis-suppressor gene product Raf-kinase inhibitor protein (RKIP) that inhibits both the Raf-1/MEK/ERK and NF-κB survival pathways implicated in EMT. Consequently, tumor cells normally exhibit a dysregulated NF-κB/Snail/RKIP circuitry that is intimately involved in the initiation of EMT and maintenance of drug resistance. Additional deregulated gene products in this circuit, such as the metastasis-suppressor phosphatase and tensin homologue (PTEN; repressed by Snail) and the putative-metastasis inducer Yin Yang (YY) 1 (target of NF-κB) also have been associated in the regulation of EMT. We recently have investigated the direct role of YY1 in the regulation of EMT. This review discusses the molecular regulation of EMT in cancer cells through the activity of the dysregulated NF-κB/Snail/ YY1/PTEN/RKIP circuitry. In addition, we propose YY1 as a potential novel prognostic biomarker for EMT and a therapeutic target for both the prevention of metastasis and the reversal of resistance.
Transcription Regulator Yin-Yang 1: From Silence to Cancer
227-238
10.1615/CritRevOncog.v16.i3-4.60
Weidong
Zhu
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Department of Medicine. Division of Dermatology. Jonsson Comprehensive Cancer Center. Geffen School of Medicine at the University of California, Los Angeles (UCLA). Los Angeles, CA,
Samuel Y.
Olson
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Department of Medicine. Division of Dermatology. Jonsson Comprehensive Cancer Center. Geffen School of Medicine at the University of California, Los Angeles (UCLA). Los Angeles, CA
Hermes
Garban
Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center
transcriptional regulation
gene expression
nitric oxide
redox regulation
zinc-finger
oxidation
Yin Yang (YY) 1 represents the epitome of what is considered to be a "Swiss army knife" transcription factor and regulator. YY1 is a ubiquitous and multifunctional zinc-finger transcription factor member of the Polycomb group protein family, a group of homeobox gene receptors that can act as activators or repressors of transcriptional activity. Furthermore, YY1 can act as a redox sensor, adaptor molecule, and chromatin structure and function regulator. YYl’s characteristic function as transcriptional activator and repressor relies on its C2H2 (x4) zinc-finger structural DNA-binding motifs tangled with 2 specific regulatory domains. This structural conformation will render the activity of YY1 susceptible to changes in cellular redox status. YY1 also has been shown to undergo chromatin remodeling via interactions with histone acetyl transferase and histone deacetylase complexes. Both groups modify histones, resulting in altered chromatin structure. Herein, we will discuss the multiple roles and mechanisms of YY1 in the regulation of gene expression, its genetic factor functions, epigenetic regulatory activity, and its role as a redox sensor in the context of malignant neoplastic diseases.
Yin Yang 2: The Great Unknown within the Yin Yang 1 Regulatory Network
239-243
10.1615/CritRevOncog.v16.i3-4.70
Martin
Klar
Charité
YY1
YY2
transcriptional regulation
The fundamental biological relevance of the transcription factor Yin Yang 1 (YY1) has been studied and described intensively in hundreds of publications. To date, however, only limited data of its structural and functional homologue YY2 are available. Especially, the impact of Yin Yang 2 (YY2) in the regulatory network of YY1 is almost unexplored. This article summarizes all critical aspects that are (or will be) relevant for a better understanding of YY1- and/or YY2-mediated cellular control mechanisms.
Yin Yang 1 in Human Cancer
245-260
10.1615/CritRevOncog.v16.i3-4.80
Sarah
Nicholson
Department of Histopathology, Manchester Royal Infirmary, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester, United Kingdom
Helen
Whitehouse
Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom
Khimara
Naidoo
Academic Foundation Programme, St Thomas’ Hospital, Guys and St Thomas’ National Health Service Foundation Trust, London, United Kingdom
Richard
Byers
University of Manchester
Yin Yang 1
carcinogenesis
prognosis
cell cycle
apoptosis
human cancer
The transcription factor Yin Yang (YY) 1 controls many divergent cellular processes, including cell proliferation and apoptosis. These are key to cancer development, as a consequence of which its expression has been studied in an increasingly wide range of human cancers, including lymphoma, breast, prostate, colon, ovarian, cervical, and brain cancers, osteosarcoma, rhabdomyosarcoma, and leukemia. It is a regulatory transcription factor for a wide range of genes, including genes involved in control of the cell cycle and apoptosis, and it can act either to upregulate or downregulate downstream gene expression, depending on the cellular environment, cofactors, and the gene targeted. Its expression has been associated with development of a malignant phenotype in some human cancers; tumor progression, including metastasis; and survival. However, as data on its prognostic significance has become available for more human cancers, its role in tumor progression has become controversial; there is conflicting data on its association with outcome, with some studies showing a favorable and others an unfavorable association. This is probably because of the many different roles YY1 plays in control of proliferation and apoptosis, one or the other of which may be more prominent in any given tumor. These studies are reviewed to give an overview of the increasingly recognized importance of YY1 in human tumorigenesis.
Overexpression of Yin Yang 1 in the Pathogenesis of Human Hematopoietic Malignancies
261-267
10.1615/CritRevOncog.v16.i3-4.90
Benjamin
Bonavida
Department of Microbiology, Immunology, &
Molecular Genetics, David Geffen School of Medicine at UCLA, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA
Sara
Huerta-Yepez
Hospital Infantil de México Federico Gomez
Stavroula
Baritaki
Center for Systems Biomedicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
Mario I.
Vega
Oncology Research Unit, Oncology Hospital Siglo XXI National Medical Center IMSS, Mexico City, Mexico; Department of Medicine, Hematology-Oncology Division, Greater Los Angeles VA Healthcare Center, David Geffen School of
Medicine, University of California, Los Angeles
H.
Liu
Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California;Experimental Research Center, China Academy of Chinese M
Haiming
Chen
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA
James R.
Berenson
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA
non-Hodgkin lymphoma
AIDS-related lymphoma
multiple myeloma
chronic lymphocytic leukemia
Yin Yang 1 prognostic factor
The transcription factor Yin Yang (YY) 1 has been reported to be overexpressed in several tumor types and plays a role in both the progression of the disease as well as the maintenance of tumor cell resistance to cell death by cytotoxic drugs. YY1 also has been reported to be a prognostic factor for several cancers and was proposed to be a therapeutic target. The expression, function, and role of YY1 in the pathogenesis of hematologic malignancies are summarized briefly herein. Data are represented for B non-Hodgkin lymphoma, AIDS-related lymphoma, multiple myeloma, and children’s acute lymphocytic leukemia.