Notch3 pathway alterations in ovarian cancer.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hu, W; Liu, T; Ivan, C; Sun, Y; Huang, J; Mangala, LS; Miyake, T; Dalton, HJ; Pradeep, S; Rupaimoole, R; Previs, RA; Han, HD; Bottsford-Miller, J; Zand, B; Kang, Y; Pecot, CV; Nick, AM; Wu, SY; Lee, J-S; Sehgal, V; Ram, P; Liu, J; Tucker, SL; Lopez-Berestein, G; Baggerly, KA; Coleman, RL; Sood, AK

Published Date

  • June 15, 2014

Published In

Volume / Issue

  • 74 / 12

Start / End Page

  • 3282 - 3293

PubMed ID

  • 24743243

Pubmed Central ID

  • 24743243

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-13-2066

Language

  • eng

Conference Location

  • United States