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Notch3 Pathway Alterations in Ovarian Cancer
- Source :
- Cancer Research. 74:3282-3293
- Publication Year :
- 2014
- Publisher :
- American Association for Cancer Research (AACR), 2014.
-
Abstract
- The Notch pathway plays an important role in the growth of high-grade serous ovarian (HGS-OvCa) and other cancers, but its clinical and biologic mechanisms are not well understood. Here, we found that the Notch pathway alterations are prevalent and significantly related to poor clinical outcome in patients with ovarian cancer. Particularly, Notch3 alterations, including amplification and upregulation, were highly associated with poor patient survival. Targeting Notch3 inhibited ovarian cancer growth and induced apoptosis. Importantly, we found that dynamin-mediated endocytosis was required for selectively activating Jagged-1–mediated Notch3 signaling. Cleaved Notch3 expression was the critical determinant of response to Notch-targeted therapy. Collectively, these data identify previously unknown mechanisms underlying Notch3 signaling and identify new, biomarker-driven approaches for therapy. Cancer Res; 74(12); 3282–93. ©2014 AACR.
- Subjects :
- Dynamins
Cancer Research
Paclitaxel
endocrine system diseases
Notch signaling pathway
Mice, Nude
Apoptosis
Kaplan-Meier Estimate
Biology
Endocytosis
Article
Transcriptome
Mice
Downregulation and upregulation
Cell Line, Tumor
medicine
Animals
Humans
Serrate-Jagged Proteins
RNA, Small Interfering
Receptor, Notch3
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms
Receptors, Notch
Calcium-Binding Proteins
Membrane Proteins
medicine.disease
Antineoplastic Agents, Phytogenic
Xenograft Model Antitumor Assays
Tumor Burden
Cell biology
Serous fluid
Oncology
Gene Knockdown Techniques
Cancer research
Intercellular Signaling Peptides and Proteins
Jagged-1 Protein
Female
Neoplasms, Cystic, Mucinous, and Serous
Ovarian cancer
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....a3fac9c594b4a9e58994a0f47f0db1f2