The TRAIL ligand is a promising anticancer agent that preferentially kills tumor cells without apparent damage to healthy cells. Many cancers exhibit resistance to TRAIL, however, thus limiting its therapeutic potential. According to a study in the March 22 issue of the Journal of Cell Biology (www.jcb.org), small molecules known to block Mcl-1 (induced myeloid leukemia cell differentiation protein) might represent a suitable means to overcome TRAIL resistance.
Researchers know that TRAIL-induced cell death entirely depends on the presence of Bax, which is a member of the proapoptotic Bcl-2 family of proteins and is often lost in tumor cells for various reasons. Despite the expression of Bak, another protein that promotes dell death, Bax-deficient cells are resistant to TRAIL-induced death.
Peter Daniel (Humboldt University, Germany) and colleagues investigate the role of two Bcl-2 proteins--Mcl-1 and Bcl-xL--that keep Bak in check. The team's findings show that blocking Mcl-1 but not Bcl-xL overcame resistance to TRAIL-induced cell death in bax-deficient cells and enabled TRAIL to activate Bak. Blocking Bak inhibitors like Mcl-1 appears to be a promising strategy in limiting the resistance of cancers to TRAIL.
About the Journal of Cell Biology
Founded in 1955, the Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org.
Gillissen, B., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200912070.