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Journal article
G1/S Cell Cycle Arrest Provides Anoikis Resistance through Erk-Mediated Bim Suppression
Molecular and cellular biology, v 25(12), pp 5282-5291
01 Jun 2005
PMID: 15923641
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Proper attachment to the extracellular matrix is essential for cell survival. Detachment from the extracellular matrix results in an apoptotic process termed anoikis. Anoikis induction in MCF-10A mammary epithelial cells is due not only to loss of survival signals following integrin disengagement, but also to consequent downregulation of epidermal growth factor (EGFR) and loss of EGFR-induced survival signals. Here we demonstrate that G
1
/S arrest by overexpression of the cyclin-dependent kinase inhibitors p16
INK4a
, p21
Cip1
, or p27
Kip1
or by treatment with mimosine or aphidicolin confers anoikis resistance in MCF-10A cells. G
1
/S arrest-mediated anoikis resistance involves suppression of the BH3-only protein Bim. Furthermore, in G
1
/S-arrested cells, Erk phosphorylation is maintained in suspension and is necessary for Bim suppression. Following G
1
/S arrest, known proteins upstream of Erk, including Raf and Mek, are not activated. However, retained Erk activation under conditions in which Raf and Mek activation is lost is observed, suggesting that G
1
/S arrest acts at the level of Erk dephosphorylation. Thus, anoikis resistance by G
1
/S arrest is mediated by a mechanism involving Bim suppression through maintenance of Erk activation. These results provide a novel link between cell cycle arrest and survival, and this mechanism could contribute to the survival of nonreplicating, dormant tumor cells that avert apoptosis during early stages of metastasis.
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Details
- Title
- G1/S Cell Cycle Arrest Provides Anoikis Resistance through Erk-Mediated Bim Suppression
- Creators
- Nicole L. Collins - Harvard UniversityMaurico J. Reginato - Harvard UniversityJessica K. Paulus - Harvard UniversityDennis C. Sgroi - Massachusetts General HospitalJoshua LaBaer - Harvard UniversityJoan S. Brugge - Harvard University
- Publication Details
- Molecular and cellular biology, v 25(12), pp 5282-5291
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000229605900041
- Scopus ID
- 2-s2.0-20344398190
- Other Identifier
- 991019174051004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology