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 language | English |
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Pages (from-to) | 162-167 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences (PNAS) |
Volume | 105 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2008 |
Keywords / Materials (for Non-textual outputs)
- molecular target
- RNAi
- tumorigenesis
- apoptosis
- BH3-only