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Mus musculus

ABSTRACT: JNK promotes epithelial cells anoikis by transcriptional and post-translational regulation of BH3-only proteins

PROVIDER: PRJNA348813 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4428790_1.fastq.gz	Fastqsanger.gz
	SRR4428790_2.fastq.gz	Fastqsanger.gz
	SRR4428781_1.fastq.gz	Fastqsanger.gz
	SRR4428781_2.fastq.gz	Fastqsanger.gz
	SRR4428791_1.fastq.gz	Fastqsanger.gz

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Gene expression of attached and suspended Bim-/- Bmf-/- murine kidney epithelial cells

Project description:Suspension-induced cell death, or anoikis, is implicated in different stages of breast development as well as tumor progression and metastasis. The pro-apoptotic BH3-only proteins BIM and BMF are known positive regulators of anoikis. We examined the gene expression changes that occur in BIM-/- BMF-/- cells during attachment and suspension. This study is supplemental to our work establishing a role for JNK in anoikis (Girnius N, Davis RJ. 2017. JNK promotes epithelial cell anoikis by transcriptional and post-translational regulation of BH3-only proteins. (2017) Cell Reports 21: 1910-1921; doi: 10.1016/j.celrep.2017.10.067)

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JNK promotes epithelial cells anoikis by transcriptional and post-translational regulation of BH3-only proteins

Project description: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.

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