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High FOXA1 levels induce ER transcriptional reprogramming, a pro-metastatic secretome, and metastasis in endocrine-resistant breast cancer.
Fu, Xiaoyong; Pereira, Resel; Liu, Chia-Chia; De Angelis, Carmine; Shea, Martin J; Nanda, Sarmistha; Qin, Lanfang; Mitchell, Tamika; Cataldo, Maria L; Veeraraghavan, Jamunarani; Sethunath, Vidyalakshmi; Giuliano, Mario; Gutierrez, Carolina; Gyorffy, Balázs; Trivedi, Meghana V; Cohen, Ofir; Wagle, Nikhil; Nardone, Agostina; Jeselsohn, Rinath; Rimawi, Mothaffar F; Osborne, C Kent; Schiff, Rachel.
  • Fu X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
  • Pereira R; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liu CC; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • De Angelis C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Clinical Medicine and Surge
  • Shea MJ; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Nanda S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Qin L; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mitchell T; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Cataldo ML; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Clinical Medicine and Surge
  • Veeraraghavan J; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Sethunath V; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Giuliano M; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
  • Gutierrez C; Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Gyorffy B; Department of Bioinformatics, Semmelweis University, 1085 Budapest, Hungary; RCNS Cancer Biomarker Research Group, Institute of Enzymology, Magyar Tudósok körútja 2, 1117 Budapest, Hungary.
  • Trivedi MV; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pharmacy Practice and Trans
  • Cohen O; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84105, Israel
  • Wagle N; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Nardone A; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA.
  • Jeselsohn R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02210, USA.
  • Rimawi MF; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  • Osborne CK; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medic
  • Schiff R; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medic
Cell Rep ; 42(8): 112821, 2023 Aug 29.
Article en En | MEDLINE | ID: mdl-37467106
ABSTRACT
Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near Secretome14 genes is also increased in mutant ER-expressing or mitogen-treated ER+ BC cells and in ER+ metastatic vs. primary tumors, suggesting a convergent pathway including high growth factor receptor signaling in activating pro-metastatic secretome genes. Our findings uncover H-FOXA1-induced ER reprogramming that drives EndoR and metastasis partly via an H-FOXA1/ER-dependent secretome.
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Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Año: 2023 Tipo del documento: Article