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J Clin Invest DOI:10.1172/JCI71545

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

Publication TypeJournal Article
Year of Publication2014
AuthorsWatanabe, H, Ma, Q, Peng, S, Adelmant, G, Swain, D, Song, W, Fox, C, Francis, JM, Pedamallu, CSekhar, DeLuca, DS, Brooks, AN, Wang, S, Que, J, Rustgi, AK, Wong, K-K, Ligon, KL, X Liu, S, Marto, JA, Meyerson, M, Bass, AJ
JournalJ Clin Invest
Date Published2014 Apr
KeywordsAdenovirus E1A Proteins, Binding Sites, Carcinoma, Squamous Cell, Cell Line, Cell Line, Tumor, Chromatiaceae, Embryonic Stem Cells, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Octamer Transcription Factor-3, Oncogenes, Pluripotent Stem Cells, Protein Binding, Proto-Oncogene Proteins, SOXB1 Transcription Factors, Transcription Factors, Transcriptome, Tumor Suppressor Proteins

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.


Alternate JournalJ. Clin. Invest.
PubMed ID24590290
PubMed Central IDPMC3973117
Grant ListP20 CA090578 / CA / NCI NIH HHS / United States
R00 DX082650 / / PHS HHS / United States
P30 DK050306 / DK / NIDDK NIH HHS / United States
P20 CA90578 / CA / NCI NIH HHS / United States
K08 CA134931 / CA / NCI NIH HHS / United States
R01 DK056645 / DK / NIDDK NIH HHS / United States
P01 CA154303 / CA / NCI NIH HHS / United States
R01 CA109038 / CA / NCI NIH HHS / United States
P01 CA098101 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
R00 DK082650 / DK / NIDDK NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States
R01 DK060694 / DK / NIDDK NIH HHS / United States