title: Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication.
abstract: The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities. Data mining from the proteomic tissue-based datasets from the Human Protein Atlas were used for protein expression patterns of YY1 and the four CSC markers in 17 types of cancer, including both solid and hematological malignancies. A close association was revealed between the frequency of expressions of YY1 and SOX2 as well as SOX2 and OCT4 in all cancers analyzed. Two types of dynamics were identified based on the nature of their association, namely, inverse or direct, between YY1 and SOX2. These two dynamics define distinctive patterns of BMI1 and OCT4 expressions. The relationship between YY1 and SOX2 expressions as well as the expressions of BMI1 and OCT4 resulted in the classification of four groups of cancers with distinct molecular signatures: (1) Prostate, lung, cervical, endometrial, ovarian and glioma cancers (YY1(lo)SOX2(hi)BMI1(hi)OCT4(hi)) (2) Skin, testis and breast cancers (YY1(hi)SOX2(lo)BMI1(hi)OCT4(hi)) (3) Liver, stomach, renal, pancreatic and urothelial cancers (YY1(lo)SOX2(lo)BMI1(hi)OCT4(hi)) and (4) Colorectal cancer, lymphoma and melanoma (YY1(hi)SOX2(hi)BMI1(lo)OCT4(hi)). A regulatory loop is proposed consisting of the cross-talk between the NF-kB/PI3K/AKT pathways and the downstream inter-regulation of target gene products YY1, OCT4, SOX2 and BMI1.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Kaufhold
authors.affiliation: NantBioScience, Inc, NantWorks, LLC & California NanoSystems Institute (CnSI), University of California Los Angeles, Los Angeles, CA, 90095, USA. hgarban@ucla.edu.
authors.forename: Hermes
authors.initials: H
authors.lastname: Garbán
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. bbonavida@mednet.ucla.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
mesh_terms: D000818:Animals; D057225:Data Mining; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D063150:Polycomb Repressive Complex 1
keywords: BMI1; Cancer stem cells; NANOG; OCT4; SOX2; Yin Yang 1