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Notch3 pathway alterations in ovarian cancer.

Publication ,  Journal Article
Hu, W; Liu, T; Ivan, C; Sun, Y; Huang, J; Mangala, LS; Miyake, T; Dalton, HJ; Pradeep, S; Rupaimoole, R; Previs, RA; Han, HD; Zand, B ...
Published in: Cancer Res
June 15, 2014

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.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2014

Volume

74

Issue

12

Start / End Page

3282 / 3293

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Burden
  • Transcriptome
  • Serrate-Jagged Proteins
  • Receptors, Notch
  • Receptor, Notch3
  • RNA, Small Interfering
  • Paclitaxel
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Hu, W., Liu, T., Ivan, C., Sun, Y., Huang, J., Mangala, L. S., … Sood, A. K. (2014). Notch3 pathway alterations in ovarian cancer. Cancer Res, 74(12), 3282–3293. https://doi.org/10.1158/0008-5472.CAN-13-2066
Hu, Wei, Tao Liu, Cristina Ivan, Yunjie Sun, Jie Huang, Lingegowda S. Mangala, Takahito Miyake, et al. “Notch3 pathway alterations in ovarian cancer.Cancer Res 74, no. 12 (June 15, 2014): 3282–93. https://doi.org/10.1158/0008-5472.CAN-13-2066.
Hu W, Liu T, Ivan C, Sun Y, Huang J, Mangala LS, et al. Notch3 pathway alterations in ovarian cancer. Cancer Res. 2014 Jun 15;74(12):3282–93.
Hu, Wei, et al. “Notch3 pathway alterations in ovarian cancer.Cancer Res, vol. 74, no. 12, June 2014, pp. 3282–93. Pubmed, doi:10.1158/0008-5472.CAN-13-2066.
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. Notch3 pathway alterations in ovarian cancer. Cancer Res. 2014 Jun 15;74(12):3282–3293.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2014

Volume

74

Issue

12

Start / End Page

3282 / 3293

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Burden
  • Transcriptome
  • Serrate-Jagged Proteins
  • Receptors, Notch
  • Receptor, Notch3
  • RNA, Small Interfering
  • Paclitaxel
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis