Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes.

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

Li Z, Zhao J, Du Y, Park HR, Sun SY, Bernal-Mizrachi L, Aitken A, Khuri FR, Fu H

Department of Pharmacology and Winship Cancer Institute, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.

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 14-3-3zeta in tumorigenesis through a mechanism that involves anoikis resistance. 14-3-3zeta 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 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 14-3-3zeta. This work not only reveals a critical role of 14-3-3zeta in anoikis suppression in lung cancer cells, but also identifies and validates 14-3-3zeta as a potential molecular target for anticancer therapeutic development.

Published 9 January 2008 in Proc Natl Acad Sci U S A, 105(1): 162-7.
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