Notch2/notch3/dll3/maml1/adam17 signaling network is associated with ovarian cancer

Abstract

Notch signaling is well-known for its role in regulating cell self-renewal and differentiation. Within the cancer research field, it has been identified that dysregulated Notch signaling is involved directly with various types of cancer. Although Notch signaling is generally considered as oncogenic, it sometimes acts as a tumor suppressor, highlighting the complexity of the role of Notch in cancer. A number of studies have associated Notch signaling components with ovarian cancer, but the underlying molecular mechanisms are not well-elucidated. In the present study, the roles of main components of Notch signaling in ovarian cancer were systematically analyzed through large data portals, including Prediction of Clinical Outcomes from Genomic Profiles, Gene Expression across Normal and Tumor tissue, CSIOVDB, Broad Institute Cancer Cell Line Encyclopedia and cBioPortal. Upregulated expression of proteins in the Notch signaling pathway components in ovarian cancer was identified to be generally associated with poor overall and disease-free survival time, and more advanced cancer stages. In addition, Notch components were enriched in ovarian cancer tissues and cell lines. These results led to a proposed neurogenic locus notch homolog protein (NOTCH)2/NOTCH3/Delta-like protein 3/Mastermind-like protein 1/a disintegrin and metalloproteinase domain-containing protein 17 network. Anticancer drugs, developed to target this network, may have high specificity in treating Notch-associated ovarian cancer.