title: SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.
abstract: The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.
authors.forename: Hideo
authors.initials: H
authors.lastname: Watanabe
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Ma
authors.forename: Shouyong
authors.initials: S
authors.lastname: Peng
authors.forename: Guillaume
authors.initials: G
authors.lastname: Adelmant
authors.forename: Danielle
authors.initials: D
authors.lastname: Swain
authors.forename: Wenyu
authors.initials: W
authors.lastname: Song
authors.forename: Cameron
authors.initials: C
authors.lastname: Fox
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Francis
authors.forename: Chandra Sekhar
authors.initials: CS
authors.lastname: Pedamallu
authors.forename: David S
authors.initials: DS
authors.lastname: DeLuca
authors.forename: Angela N
authors.initials: AN
authors.lastname: Brooks
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Que
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
authors.forename: Kwok-kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002841:Chromatiaceae / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D009857:Oncogenes; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins