Not all NOTCH Is Created Equal: The Oncogenic Role of NOTCH2 in Bladder Cancer and Its Implications for Targeted Therapy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Tetsutaro HayashiPeter C Black

Abstract

Recent molecular analyses of bladder cancer open the door to significant advances in targeted therapies. NOTCH has been identified as a tumor suppressor in bladder cancer, but prior reports have focused on NOTCH1 Here we hypothesized that NOTCH2 is an oncogene suitable for therapeutic targeting in bladder cancer. We studied genomic aberrations of NOTCH, compared survival and tumor progression according to NOTCH2 expression levels, and studied NOTCH2 function in vitro and vivo We report a high rate of NOTCH2 copy number gain in bladder cancer. High NOTCH2 expression was identified especially in the basal subtype and in mesenchymal tumors. NOTCH2 activation correlated with adverse disease parameters and worse prognosis by immunohistochemistry. Forced overexpression of the intracellular domain of NOTCH2 (N2ICD) induced cell growth and invasion by cell-cycle progression, maintenance of stemness and epithelial-to-mesenchymal transition (EMT). These effects were abrogated by silencing of CSL, indicating that the effects were mediated through the canonical NOTCH signaling pathway. In an orthotopic xenograft model, forced overexpression of N2ICD increased growth, invasion, and metastasis. To explore the potential for therapeutic target...Continue Reading

References

Dec 14, 2001·The Journal of Biological Chemistry·Tatsuya IsoLarry Kedes
Nov 3, 2004·Cancer Research·Xing FanCharles G Eberhart
Feb 3, 2005·Molecular and Cellular Biology·Borja BelandiaMalcolm G Parker
Jul 7, 2005·The Journal of Experimental Medicine·Leonor M SarmentoNadia Carlesso
Nov 18, 2005·Blood·Kevin G Leong, Aly Karsan
Mar 3, 2007·Cancer Research·Ie-Ming Shih, Tian-Li Wang
May 21, 2009·British Journal of Cancer·M TanakaS Komiya
Apr 16, 2010·Nature·Yan WuChristian W Siebel
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pawel K MazurJens T Siveke
Apr 22, 2011·Nature Reviews. Cancer·Prathibha RanganathanAnthony J Capobianco
Aug 11, 2011·Development·Emma R AnderssonUrban Lendahl
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicholas J WangRaymond J Cho
Feb 15, 2012·The International Journal of Biochemistry & Cell Biology·Yosuke MatsunoCory M Hogaboam
May 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gottfrid SjödahlMattias Höglund
Jul 10, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ann Marie Egloff, Jennifer R Grandis
May 10, 2013·Molecular Cancer Therapeutics·Kilian M GustPeter C Black
Jan 31, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey S DamrauerWilliam Y Kim
Aug 30, 2014·BMC Cancer·Annemarie GreifeWolfgang A Schulz
Sep 10, 2014·Nature Medicine·Theodoros RampiasApostolos Klinakis
Dec 24, 2014·Nature Reviews. Cancer·Margaret A Knowles, Carolyn D Hurst
Jan 13, 2015·The Journal of Clinical Investigation·Antonio MaraverManuel Serrano

❮ Previous
Next ❯

Citations

Dec 31, 2016·International Journal of Molecular Sciences·Catia GiovanniniLaura Gramantieri
Aug 11, 2017·Physiological Reviews·Chris Siebel, Urban Lendahl
Feb 3, 2016·Nature Reviews. Urology·Annette Fenner
Apr 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zheng ZhouFei Shi
Apr 21, 2017·Oncotarget·Weerachai JaratlerdsiriVanessa M Hayes
Jun 28, 2016·Oncology Letters·Jie LuChuanyong Guo
Dec 12, 2018·Cancer Biomarkers : Section a of Disease Markers·Hailong SuJuan Meng
Oct 28, 2017·Chemical Biology & Drug Design·Peter DobranowskiPeter C Black
Jan 27, 2019·Nature Protocols·Guadalupe Lorenzatti HilesMark L Day
Jun 5, 2019·Journal of Translational Medicine·F LessiC M Mazzanti
May 30, 2019·Cancers·Masahiro Shibata, Mohammad Obaidul Hoque
Nov 9, 2019·Journal of Experimental & Clinical Cancer Research : CR·You ZouShi-Ming Chen
Sep 19, 2020·Molecular & Cellular Oncology·Pavlos MsaouelNizar M Tannir
Jun 7, 2017·International Journal of Molecular Medicine·Yuwei YeYongning Zhou
Apr 13, 2018·Nature Reviews. Urology·Akihiro GorikiPeter C Black
Oct 9, 2020·Signal Transduction and Targeted Therapy·Siyuan QinWeifeng He
Aug 28, 2020·Molecular Cancer Therapeutics·Yoshihisa KawaiMartin E Gleave
Jul 29, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qiaofen FuWeiyi Fang
Jan 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Lingyun ZhangHan Luo
Jan 17, 2021·International Journal of Molecular Sciences·Javier Torres-JiménezJavier Molina-Cerrillo
Jan 1, 2021·Experimental Cell Research·Rui-Huan GanYou-Guang Lu
Mar 7, 2021·Cancers·Dorota AnusewiczAndrzej K Bednarek
Apr 17, 2021·Seminars in Cancer Biology·Antonio Ferreira, Jon C Aster
Aug 19, 2021·The Journal of Nutritional Biochemistry·Hua WeiDa-Li Zheng
Aug 21, 2021·Journal of Zhejiang University. Science. B·Wenwen ZhongJianguang Qiu
Nov 24, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Inesa ThomsenPierangela Sabbattini

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