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

Z. G. Li, J. Zhao, Y. H. Du, H. R. Park, S. Y. Sun, L. Bernal-Mizrachi, A. Aitken, F. R. Khuri, H. A. Fu

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 14-3-3 in tumorigenesis through a mechanism that involves anoikis resistance. 114-3-3 zeta 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 zeta 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 upregulated 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 14-3-3 zeta. This work not only reveals a critical role of 14-3-3 zeta in anoikis suppression in lung cancer cells, but also identifies and validates 114-3-3 zeta as a potential molecular target for anticancer therapeutic development.
Original languageEnglish
Pages (from-to)162-167
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Volume105
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords / Materials (for Non-textual outputs)

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

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