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An Orthotopic Bladder Cancer Model for Gene Delivery Studies
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Not all NOTCH Is Created Equal: The Oncogenic Role of NOTCH2 in Bladder Cancer and Its Implications for Targeted

Tetsutaro Hayashi1, Kilian M Gust2, Alexander W Wyatt2

  • 1The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. Department of Urology, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 16, 2016
PubMed
Abstract

Insights

NOTCH2 functions as an oncogene in bladder cancer, promoting tumor growth and metastasis. Inhibiting NOTCH2 presents a promising new therapeutic strategy for invasive bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Molecular analyses reveal potential for targeted therapies in bladder cancer.
  • NOTCH signaling is implicated in cancer, with prior research focusing on NOTCH1.

Purpose of the Study:

  • To investigate the role of NOTCH2 as an oncogene in bladder cancer.
  • To explore NOTCH2 as a potential therapeutic target for bladder cancer.

Main Methods:

  • Studied genomic aberrations and NOTCH2 expression levels in bladder cancer.
  • Assessed NOTCH2 function in vitro and in vivo using cell culture and xenograft models.
  • Investigated therapeutic targeting by silencing NOTCH2 and using inhibitory antibodies.

Main Results:

  • High NOTCH2 copy number gain and expression observed in bladder cancer, particularly in basal and mesenchymal subtypes.
  • NOTCH2 activation correlated with adverse disease parameters and poor prognosis.
  • NOTCH2 overexpression promoted cell growth, invasion, and metastasis via cell-cycle progression, stemness, and epithelial-to-mesenchymal transition (EMT).
  • NOTCH2 inhibition reduced tumor growth, invasion, and metastasis in vitro and in vivo.

Conclusions:

  • NOTCH2 acts as an oncogene promoting bladder cancer progression through EMT, cell-cycle, and stemness.
  • Inhibition of NOTCH2 represents a rational and novel treatment strategy for invasive bladder cancer.

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