Journal article
Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis
Nature cell biology, v 5(8), pp 733-740
Aug 2003
PMID: 12844146
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epithelial cells must adhere to the extracellular matrix (ECM) for survival, as detachment from matrix triggers apoptosis or anoikis. Integrins are major mediators of adhesion between cells and ECM proteins, and transduce signals required for cell survival. Recent evidence suggests that integrin receptors are coupled to growth factor receptors in the regulation of multiple biological functions; however, mechanisms involved in coordinate regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we identify the pro-apoptotic protein Bim as a critical mediator of anoikis in epithelial cells. Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis. Detachment-induced expression of Bim requires a lack of β1-integrin engagement, downregulation of EGF receptor (EGFR) expression and inhibition of Erk signalling. Overexpressed EGFR was uncoupled from integrin regulation, resulting in the maintenance of Erk activation in suspension, and a block in Bim expression and anoikis. Thus, Bim functions as a key sensor of integrin and growth factor signals to the Erk pathway, and loss of such coordinate regulation may contribute to tumour progression.
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Details
- Title
- Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis
- Creators
- Jessica K Paulus - Department of Cell Biology, Harvard Medical SchoolJoan S Brugge - Department of Cell Biology, Harvard Medical SchoolMauricio J Reginato - Department of Cell Biology, Harvard Medical SchoolKenna R Mills - Department of Cell Biology, Harvard Medical SchoolJayanta Debnath - Department of Cell Biology, Harvard Medical SchoolDanielle K Lynch - Department of Cell Biology, Harvard Medical SchoolDennis C Sgroi - Department of Pathology, Harvard Medical School, Massachusetts General HospitalSenthil K Muthuswamy - Department of Cell Biology, Harvard Medical School Cold Spring Harbor Laboratory
- Publication Details
- Nature cell biology, v 5(8), pp 733-740
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000311590900017
- Scopus ID
- 2-s2.0-0042696985
- Other Identifier
- 991014878051804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Environmental Sciences
- Environmental Studies
- Meteorology & Atmospheric Sciences