Exploring the role of JNK in cancer and anoikis.

Nomeda Girnius, University of Massachusetts, USA

The c-Jun N-terminal Kinase (JNK) pathway plays a role in many cellular processes, so it is not surprising that this pathway has been implicated in cancer and development. Previous work suggested that Jnk1 and Jnk2 may be tumor suppressors in the mouse mammary gland, but the mechanism of this suppression had not been determined. Given that loss of JNK in the mammary gland led to ductal occlusion, we hypothesized that the pathway may be important for cells to undergo detachment-induced apoptosis, or anoikis. We have found that JNK loss in vitro increases cell survival in suspension culture. Loss of BH3-only proteins Bim and Bmf also causes ductal infilling in vivo and increases survival in suspension culture. However, point mutants of the the phosphorylation sites targetd by JNK on Bim and Bmf do not appear to have increased survival in suspension, and they fail to recapitulate the in vivo phenotype observed in JNK-deficient mammary glands. Thus, it is likely that JNK is acting through an alternative pathway to mediate anoikis in vitro and in vivo.