Abstract
Protection from detachment-induced cell death, termed anoikis, facilitates metastasis. Though anoikis is largely attributed to the loss of integrin-related ‘outside-in’ survival signals, Terada and colleagues demonstrate a novel ‘inside-out’ attachment sensing role for the adapter protein p66Shc in promoting anoikis and suppressing metastasis via Ras-dependent control of proliferation and survival.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Negative feedback loop between p66Shc and ZEB1 regulates fibrotic EMT response in lung cancer cells
Cell Death & Disease Open Access 02 April 2015
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE . (1997). Geometric control of cell life and death. Science 276: 1425–1428.
Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS . (2002). The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111: 29–40.
Douma S, van Laar T, Zevenhoven J, Meuwissen R, van Garderen E, Peeper DS . (2004). Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430: 1034–1039.
Frisch SM, Francis H . (1994). Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124: 619–626.
Gilmore AP . (2005). Anoikis. Cell Death Differ 12 (Suppl 2): 1473–1477.
Ma Z, Liu Z, Wu R-F, Terada LS . (2010). p66Shc restrains Ras hyperactivation and suppresses metastatic behavior. Oncogene 29: 5559–5567.
Ma Z, Myers DP, Wu RF, Nwariaku FE, Terada LS . (2007). p66Shc mediates anoikis through RhoA. J Cell Biol 179: 23–31.
Mailleux AA, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge JS . (2007). BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell 12: 221–234.
Pinton P, Rizzuto R . (2008). p66Shc, oxidative stress and aging: importing a lifespan determinant into mitochondria. Cell Cycle 7: 304–308.
Re F, Zanetti A, Sironi M, Polentarutti N, Lanfrancone L, Dejana E et al. (1994). Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells. J Cell Biol 127: 537–546.
Acknowledgements
JD is supported by Grants from the NIH (RO1CA126792; CA126792-S1 ARRA) and the California Tobacco Related Disease Research Program (18XT-0106).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no conflict of interest.
Rights and permissions
About this article
Cite this article
Debnath, J. p66Shc and Ras: controlling anoikis from the inside-out. Oncogene 29, 5556–5558 (2010). https://doi.org/10.1038/onc.2010.347
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/onc.2010.347
This article is cited by
-
Negative feedback loop between p66Shc and ZEB1 regulates fibrotic EMT response in lung cancer cells
Cell Death & Disease (2015)
-
The G Protein-Coupled Estrogen Receptor-1, GPER-1, Promotes Fibrillogenesis via a Shc-Dependent Pathway Resulting in Anchorage-Independent Growth
Hormones and Cancer (2014)