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Author Notes:

To whom correspondence should be addressed: Haian Fu (Email: hfu@emory.edu)

Communicated by R. John Collier, Harvard Medical School, Boston, MA, November 19, 2007

Author contributions: F.R.K. and H.F. designed research; Z.L., J.Z., Y.D., H.R.P., and L.B.-M. performed research; S.-Y.S. and A.A. contributed new reagents/analytic tools; Z.L., J.Z., Y.D., H.R.P., S.-Y.S., F.R.K., and H.F. analyzed data; and Z.L., F.R.K., and H.F. wrote the paper.

Present address: Hae Ryoun Park, Department of Oral Pathology, School of Dentistry, Pusan National University, Pusan 602-739, South Korea.

We thank members of H.F.'s laboratory for helpful discussions and Anthea Hammond for editing.

The authors declare no conflict of interest.


Research Funding:

This work was supported in part by National Institutes of Health Grants R01 GM53165 (to H.F.) and P01 CA116676 (to F.R.K., H.F., and S.S.), Emory University Research Committee, and Golfers Against Cancer.

F.R.K., S.S., and H.F. are Georgia Cancer Coalition Distinguished Scholars.

H.F. is a Georgia Research Alliance Distinguished Investigator.

Y.D. is an Emory Drug Development and Pharmacogenomics Academy Fellow.


  • molecular target
  • RNAi
  • tumorigenesis
  • apoptosis
  • BH3-only

Down-regulation of 14-3-3ζ suppresses anchorage-independent growth of lung cancer cells through anoikis activation


Journal Title:

Proceedings of the National Academy of Sciences


Volume 105, Number 1


, Pages 162-167

Type of Work:

Article | Post-print: After Peer Review


The family of 14-3-3 proteins has emerged as critical regulators of diverse cellular responses under both physiological and pathological conditions. Here, we report an important role of 14-3-3ζ in tumorigenesis through a mechanism that involves anoikis resistance. 14-3-3ζ is up-regulated in a number of cancer types, including lung cancer. Through an RNAi approach using human lung adenocarcinoma-derived A549 cells as a model system, we have found that knockdown of a single ζ isoform of 14-3-3 is sufficient to restore the sensitivity of cancer cells to anoikis and impair their anchorage-independent growth. Enhanced anoikis appears to be mediated in part by up-regulated BH3-only proteins, Bad and Bim, coupled with decreased Mcl-1, resulting in the subsequent activation of Bax. This study suggests a model in which anchorage-independent growth of lung cancer cells requires the presence of 14-3-3ζ. This work not only reveals a critical role of 14-3-3ζ in anoikis suppression in lung cancer cells, but also identifies and validates 14-3-3ζ as a potential molecular target for anticancer therapeutic development.

Copyright information:

© 2007 by The National Academy of Sciences of the USA

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