SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas
Hideo Watanabe, … , Matthew Meyerson, Adam J. Bass
Hideo Watanabe, … , Matthew Meyerson, Adam J. Bass
Published March 3, 2014
Citation Information: J Clin Invest. 2014;124(4):1636-1645. https://doi.org/10.1172/JCI71545.
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Research Article Oncology

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

Hideo Watanabe, Qiuping Ma, Shouyong Peng, Guillaume Adelmant, Danielle Swain, Wenyu Song, Cameron Fox, Joshua M. Francis, Chandra Sekhar Pedamallu, David S. DeLuca, Angela N. Brooks, Su Wang, Jianwen Que, Anil K. Rustgi, Kwok-kin Wong, Keith L. Ligon, X. Shirley Liu, Jarrod A. Marto, Matthew Meyerson, Adam J. Bass

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Figure 1

SOX2 genomic occupancy in SCC cells is distinct from that in ES cells.

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SOX2 genomic occupancy in SCC cells is distinct from that in ES cells. (...
(A) Correlation matrix depicting pairwise comparisons of identified SOX2 binding peaks in the 3 SOX2-amplified SCC lines and in the ES cell line H9. Color scale represents degree of correlation (red, positive; blue, inverse). (B) Appearance of OCT4 DNA binding motif, plotted around the SOX2 motif near the summit of SOX2 binding peaks in the H9 ES cell line and in the 3 SCC lines. The OCT4 motif was highly enriched within 10 bp from the SOX2 motif in SOX2 peaks in H9 cells, but not in the SCC lines. (C) OCT4 protein expression in H9 ES cells and the 3 SCC lines. OCT4 expression was not detectable in any of the SCC lines by immunoblots.