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YAP1 maintains active chromatin state in head and neck squamous cell carcinomas that promotes tumorigenesis through cooperation with BRD4.
Chen, Nana; Golczer, Gabriel; Ghose, Subhoshree; Lin, Brian; Langenbucher, Adam; Webb, Jason; Bhanot, Haymanti; Abt, Nicholas B; Lin, Derrick; Varvares, Mark; Sattler, Martin; Egloff, Ann Marie; Joh, Richard; Uppaluri, Ravindra; Emerick, Kevin S; Lawrence, Michael S; Saladi, Srinivas Vinod.
Afiliación
  • Chen N; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA.
  • Golczer G; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Ghose S; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA.
  • Lin B; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Langenbucher A; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Webb J; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA.
  • Bhanot H; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Abt NB; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA.
  • Lin D; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Varvares M; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Sattler M; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Egloff AM; Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Joh R; Department of Physics, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23284, USA.
  • Uppaluri R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Emerick KS; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Lawrence MS; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Saladi SV; Department of Otolaryngology Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Head and Neck Lab, 20 Staniford Street 2W, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: srinivasvinod_saladi@meei.harvard.edu.
Cell Rep ; 39(11): 110970, 2022 06 14.
Article en En | MEDLINE | ID: mdl-35705032
ABSTRACT
Analysis of The Cancer Genome Atlas and other published data of head and neck squamous cell carcinoma (HNSCC) reveals somatic alterations of the Hippo-YAP pathway in approximately 50% of HNSCC. Better strategies to target the YAP1 transcriptional complex are sought. Here, we show that FAT1, an upstream inhibitor of YAP1, is mutated either by missense or by truncating mutation in 29% of HNSCC. Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibits selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Proteínas de Ciclo Celular / Proteínas Señalizadoras YAP / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Proteínas de Ciclo Celular / Proteínas Señalizadoras YAP / Neoplasias de Cabeza y Cuello Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos