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Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells.
Tornillo, Giusy; Knowlson, Catherine; Kendrick, Howard; Cooke, Joe; Mirza, Hasan; Aurrekoetxea-Rodríguez, Iskander; Vivanco, Maria D M; Buckley, Niamh E; Grigoriadis, Anita; Smalley, Matthew J.
Afiliación
  • Tornillo G; European Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Cardiff CF24 4HQ, UK.
  • Knowlson C; Centre for Cancer Research and Cell Biology, Queens University Belfast, 97 Lisburn Rd, Belfast BT9 7AE, UK.
  • Kendrick H; European Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Cardiff CF24 4HQ, UK.
  • Cooke J; European Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Cardiff CF24 4HQ, UK.
  • Mirza H; School of Cancer & Pharmaceutical Sciences, CRUK King's Health Partners Centre, King's College London, Innovation Hub, Comprehensive Cancer Centre at Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
  • Aurrekoetxea-Rodríguez I; Center for Cooperative Research in Biosciences, CIC bioGUNE, 48160 Derio, Spain.
  • Vivanco MDM; Center for Cooperative Research in Biosciences, CIC bioGUNE, 48160 Derio, Spain.
  • Buckley NE; School of Pharmacy and Centre for Cancer Research and Cell Biology, Queens University Belfast, 97 Lisburn Rd, Belfast BT9 7AE, UK.
  • Grigoriadis A; School of Cancer & Pharmaceutical Sciences, CRUK King's Health Partners Centre, King's College London, Innovation Hub, Comprehensive Cancer Centre at Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
  • Smalley MJ; European Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Cardiff CF24 4HQ, UK. Electronic address: smalleymj@cardiff.ac.uk.
Cell Rep ; 25(13): 3674-3692.e10, 2018 12 26.
Article en En | MEDLINE | ID: mdl-30590041
The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the Δaa25-45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms-uncoupling from upstream signals and splice isoform ratios-drive the activity of LYN in aggressive breast cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Familia-src Quinasas Límite: Adolescent / Adult / Animals / Female / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Familia-src Quinasas Límite: Adolescent / Adult / Animals / Female / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos