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Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs.
Gui, Jun; Zahedi, Farima; Ortiz, Angelica; Cho, Christina; Katlinski, Kanstantsin V; Alicea-Torres, Kevin; Li, Jinyang; Todd, Leslie; Zhang, Hongru; Beiting, Daniel P; Sander, Cindy; Kirkwood, John M; Snow, Bryan E; Wakeham, Andrew C; Mak, Tak W; Diehl, J Alan; Koumenis, Constantinos; Ryeom, Sandra W; Stanger, Ben Z; Puré, Ellen; Gabrilovich, Dmitry I; Fuchs, Serge Y.
Afiliación
  • Gui J; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Zahedi F; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ortiz A; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Cho C; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Katlinski KV; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Alicea-Torres K; Immunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA, USA.
  • Li J; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Todd L; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Zhang H; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Beiting DP; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Sander C; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Kirkwood JM; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Snow BE; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Wakeham AC; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Mak TW; The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Diehl JA; Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Koumenis C; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ryeom SW; Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Stanger BZ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Puré E; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Gabrilovich DI; Immunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA, USA.
  • Fuchs SY; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. syfuchs@upenn.edu.
Nat Cancer ; 1(6): 603-619, 2020 06.
Article en En | MEDLINE | ID: mdl-34124690
Primary tumor-derived factors (TDFs) act upon normal cells to generate a pre-metastatic niche, which promotes colonization of target organs by disseminated malignant cells. Here we report that TDFs-induced activation of the p38α kinase in lung fibroblasts plays a critical role in the formation of a pre-metastatic niche in the lungs and subsequent pulmonary metastases. Activation of p38α led to inactivation of type I interferon signaling and stimulation of expression of fibroblast activation protein (FAP). FAP played a key role in remodeling of the extracellular matrix as well as inducing the expression of chemokines that enable lung infiltration by neutrophils. Increased activity of p38 in normal cells was associated with metastatic disease and poor prognosis in human melanoma patients whereas inactivation of p38 suppressed lung metastases. We discuss the p38α-driven mechanisms stimulating the metastatic processes and potential use of p38 inhibitors in adjuvant therapy of metastatic cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido