Your browser doesn't support javascript.
loading
Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.
Li, Li-Yan; Yang, Qian; Jiang, Yan-Yi; Yang, Wei; Jiang, Yuan; Li, Xiang; Hazawa, Masaharu; Zhou, Bo; Huang, Guo-Wei; Xu, Xiu-E; Gery, Sigal; Zhang, Ying; Ding, Ling-Wen; Ho, Allen S; Zumsteg, Zachary S; Wang, Ming-Rong; Fullwood, Melissa J; Freedland, Stephen J; Meltzer, Stephen J; Xu, Li-Yan; Li, En-Min; Koeffler, H Phillip; Lin, De-Chen.
Afiliación
  • Li LY; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China. lly170@126.com.
  • Yang Q; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. lly170@126.com.
  • Jiang YY; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Yang W; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Jiang Y; Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Li X; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Hazawa M; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.
  • Zhou B; Cell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.
  • Huang GW; Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Xu XE; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Gery S; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China.
  • Zhang Y; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ding LW; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Ho AS; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Zumsteg ZS; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Wang MR; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Fullwood MJ; State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Freedland SJ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Meltzer SJ; Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA and the Durham VA Medical Center, Durham, NC, USA.
  • Xu LY; Departments of Medicine and Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Li EM; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China. lyxu@stu.edu.cn.
  • Koeffler HP; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China. nmli@stu.edu.cn.
  • Lin DC; Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Nat Commun ; 12(1): 4362, 2021 07 16.
Article en En | MEDLINE | ID: mdl-34272396
Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Neoplasias Esofágicas / Carcinoma de Células Escamosas / Proteínas Supresoras de Tumor / Proteína 1 de Unión a los Elementos Reguladores de Esteroles / Factores de Transcripción de Tipo Kruppel / Metabolismo de los Lípidos / Neoplasias de Cabeza y Cuello / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Neoplasias Esofágicas / Carcinoma de Células Escamosas / Proteínas Supresoras de Tumor / Proteína 1 de Unión a los Elementos Reguladores de Esteroles / Factores de Transcripción de Tipo Kruppel / Metabolismo de los Lípidos / Neoplasias de Cabeza y Cuello / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido