UMMS Affiliation

Program in Molecular Medicine; UMass Metabolic Network; Davis Lab

Publication Date

11-14-2017

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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.

Keywords

BAK, BAX, BH3-only protein, BIM, BMF, JNK, anoikis, apoptosis, epithelial cell, mammary gland

Rights and Permissions

© 2017 The Author(s).

DOI of Published Version

10.1016/j.celrep.2017.10.067

Source

Cell Rep. 2017 Nov 14;21(7):1910-1921. doi: 10.1016/j.celrep.2017.10.067. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

29141222

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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