Program in Molecular Medicine; UMass Metabolic Network; Davis Lab
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that JNK acts through a BAK/BAX-dependent apoptotic pathway by increasing BIM expression and phosphorylating BMF, leading to death of detached epithelial cells.
BAK, BAX, BH3-only protein, BIM, BMF, JNK, anoikis, apoptosis, epithelial cell, mammary gland
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© 2017 The Author(s).
DOI of Published Version
Cell Rep. 2017 Nov 14;21(7):1910-1921. doi: 10.1016/j.celrep.2017.10.067. Link to article on publisher's site
Girnius N, Davis RJ. (2017). JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins. UMass Metabolic Network Publications. https://doi.org/10.1016/j.celrep.2017.10.067. Retrieved from https://escholarship.umassmed.edu/metnet_pubs/142
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