Notch3 signaling promotes tumor cell adhesion and progression in a murine epithelial ovarian cancer model.

PloS One
Jessica C PriceJan K Kitajewski

Abstract

High grade serous ovarian cancer (HGSC) is the most common and deadly type of ovarian cancer, largely due to difficulties in early diagnosis and rapid metastasis throughout the peritoneal cavity. Previous studies have shown that expression of Notch3 correlates with worse prognosis and increased tumorigenic cell behaviors in HGSC. We investigated the mechanistic role of Notch3 in a model of metastatic ovarian cancer using the murine ovarian surface epithelial cell line, ID8 IP2. Notch3 was activated in ID8 IP2 cells via expression of the Notch3 intracellular domain (Notch3IC). Notch3IC ID8 IP2 cells injected intraperitoneally caused accelerated ascites and reduced survival compared to control ID8 IP2, particularly in early stages of disease. We interrogated downstream targets of Notch3IC in ID8 IP2 cells by RNA sequencing and found significant induction of genes that encode adhesion and extracellular matrix proteins. Notch3IC ID8 IP2 showed increased expression of ITGA1 mRNA and cell-surface protein. Notch3IC-mediated increase of ITGA1 was also seen in two human ovarian cancer cells. Notch3IC ID8 IP2 cells showed increased adhesion to collagens I and IV in vitro. We propose that Notch3 activation in ovarian cancer cells causes i...Continue Reading

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Methods Mentioned

BETA
RNA-Seq
flow cytometry
electrophoresis
Fluorescence
pulldown
Assay

Software Mentioned

Database for Annotation , Visualization and Integrated Discove...
DAVID
GSEA
TopHat
Gene Set Enrichment Analysis ( GSEA )
bcl2fastq
Graphpad Prism
DEseq
ImageJ
KMplot

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