| Literature DB >> 24743243 |
Wei Hu1, Tao Liu1, Cristina Ivan2, Yunjie Sun1, Jie Huang1, Lingegowda S Mangala2, Takahito Miyake1, Heather J Dalton1, Sunila Pradeep1, Rajesh Rupaimoole1, Rebecca A Previs1, Hee Dong Han1, Justin Bottsford-Miller1, Behrouz Zand1, Yu Kang1, Chad V Pecot1, Alpa M Nick1, Sherry Y Wu1, Ju-Seog Lee1, Vasudha Sehgal1, Prahlad Ram1, Jinsong Liu1, Susan L Tucker1, Gabriel Lopez-Berestein3, Keith A Baggerly1, Robert L Coleman1, Anil K Sood4.
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. ©2014 American Association for Cancer Research.Entities:
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Year: 2014 PMID： 24743243 PMCID： PMC4058356 DOI： 10.1158/0008-5472.CAN-13-2066
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701