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HSF1 impulsa un programa de transcripción distinto del choque térmico para apoyar los cánceres humanos altamente
Marc L Mendillo1, Sandro Santagata, Martina Koeva
1The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|August 7, 2012
Resumen
El factor de choque térmico 1 (HSF1) impulsa el cáncer mediante la regulación única de genes más allá de las proteínas de choque térmico. Este programa de cáncer HSF1 es activo en los tumores y está relacionado con la metástasis y la muerte del paciente.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Oncología Oncología.
- Genética La genética.
Sus antecedentes:
- El factor de choque térmico 1 (HSF1) es un regulador maestro de la respuesta al choque térmico.
- HSF1 está implicado en la transformación maligna, la supervivencia de las células cancerosas y la proliferación.
- La red transcripcional precisa que controla HSF1 en la malignidad y su relación con la respuesta al choque térmico siguen sin definirse.
Objetivo del estudio:
- Definir el programa transcripcional regulado por HSF1 específico para las células altamente malignas.
- Para investigar la relación entre este programa y la respuesta canónica al choque térmico.
- Evaluar la actividad y la importancia pronóstica de este programa en cánceres humanos.
Principales métodos:
- Análisis comparativo de células con potencial maligno variable y sus contrapartes no transformadas.
- Perfiles transcriptómicos para identificar genes regulados por HSF1.
- Análisis de la actividad del programa HSF1 en muestras de tumores derivadas de pacientes (mama, colon, pulmón).
Principales resultados:
- Se identificó un programa transcripcional regulado por HSF1, distinto del choque térmico, en células altamente malignas.
- Este programa específico para el cáncer incluye genes involucrados en la regulación del ciclo celular, la señalización, el metabolismo, la adhesión y la traducción.
- Si bien los genes de la proteína de choque térmico (HSP) forman parte de este programa, muchos están regulados de manera única en la malignidad.
- El programa de cáncer HSF1 es activo en tumores humanos de mama, colon y pulmón y se correlaciona con metástasis y mortalidad.
Conclusiones:
- HSF1 activamente recablea el transcriptoma durante la tumorigénesis, estableciendo un programa de cáncer distinto.
- Este programa impulsado por HSF1 tiene implicaciones pronósticas significativas para la metástasis del cáncer y la supervivencia del paciente.
- Los hallazgos sugieren posibles estrategias terapéuticas dirigidas al programa de cáncer HSF1.
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