Notch3 Interactome Analysis Identified WWP2 as a Negative Regulator of Notch3 Signaling in Ovarian Cancer

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Notch pathway is important for many cellular activities, and its dysregulation leads to several diseases in humans, including cancer. Although Notch hyperactivity has been observed in many types of cancers, the interactome of Notch receptor remains largely unknown, especially for Notch3, which is involved in ovarian cancer pathogenesis. This article is the first study, to our knowledge, that delineates the Notch3 interacting network, and demonstrates that one of the Notch3 interacting proteins, WWP2, an E3 ubiquitin-protein ligase, plays a major role in negative regulation of Notch3 signaling in cancer cells. WWP2 locus was found to be deleted, and its mRNA down-regulated in a significant fraction of ovarian carcinomas. Ectopic expression of WWP2 reduced tumorigenicity of ovarian cancer cells, and counteracted Notch3-mediated phenotypes, including promotion of cancer stem-like cell phenotype and platinum resistance, further supporting its tumor suppressor role. The results from this study provide new insights into how Notch3 signaling contributes to cancer development, and should have implications for the design of Notch3-based cancer therapy.

Vyšlo v časopise: Notch3 Interactome Analysis Identified WWP2 as a Negative Regulator of Notch3 Signaling in Ovarian Cancer. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004751
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004751

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