RESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas E1A de Adenovirus/genética , Sitios de Unión/genética , Línea Celular , Línea Celular Tumoral , Chromatiaceae/genética , Chromatiaceae/metabolismo , Células Madre Embrionarias/metabolismo , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica , Humanos , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Oncogenes , Células Madre Pluripotentes/metabolismo , Unión Proteica , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ets , TranscriptomaRESUMEN
Healthcare assistants (HCAs) play an increasingly important role in the provision of patient care and are well-placed to witness and challenge poor practice, yet often lack the confidence to do so. This article assesses the success of a two-day training course to empower HCAs to question their colleagues about practice, and the implications of this course for senior nurses.
