Heterogeneity of Jagged1 expression in human and mouse intestinal tumors: implications for targeting Notch signaling

Oncogene
S GuilmeauL H Augenlicht

Abstract

Inhibition of Notch signaling is effective in inhibiting colon tumorigenesis, but targeting specific components of the pathway may provide more effective strategies. Here we show that the expression of Jagged1, a ligand for canonical Notch signaling, was restricted to enteroendocrine cells or undetectable in the mucosa of the human small and large intestine, respectively. In contrast, increased expression characterized half of human colon tumors, although not all tumors with elevated Wnt signaling displayed elevated Jagged1. Increased Jagged1 was also present in intestinal tumors of Apc(1638N/+) and Apc(Min/+) mice, but to a higher level and more frequently in the former, and in 90% of mouse tumors Notch signaling was elevated when Jagged1 was elevated. In the human HT29Cl16E colonic carcinoma cell line, induction of goblet cell differentiation by contact inhibition of growth depended on the loss of Jagged1-mediated Notch activation, with signaling through Notch1 and Notch2 acting redundantly. Therefore, targeting of Jagged1 could be effective in downregulating Notch signaling in a subset of tumors, but may avoid the limiting gastrointestinal toxicity caused by pharmacological inhibition of Notch signaling.

References

Sep 28, 1995·Nature·S JarriaultA Israel
Oct 21, 1994·Cell·M E Fortini, S Artavanis-Tsakonas
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·R FoddeP M Khan
Dec 30, 1999·Nature Genetics·J JensenO D Madsen
Apr 17, 2001·Journal of Molecular Neuroscience : MN·J L Martys-ZageS S Sisodia
Jun 7, 2002·Genes & Development·Christy J FryerKatherine A Jones
Mar 23, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Guy R Sander, Barry C Powell
Jun 17, 2005·Nature·Silvia FreSpyros Artavanis-Tsakonas
Jul 27, 2005·Biochemical Society Transactions·J V McCarthy
Aug 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ben Z StangerDouglas A Melton
Oct 26, 2005·Biochemical Society Transactions·L CallinanJ J Mackrill
Dec 13, 2005·Nature·Benjamin Ohlstein, Allan Spradling
Jul 16, 2008·Advances in Cancer Research·Silvia FreDaniel Louvard
Jul 16, 2008·Gastroenterology·Sandra GuilmeauLeonard H Augenlicht
Dec 17, 2008·Molecular Cancer Research : MCR·Amr M GhalebVincent W Yang
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Silvia FreDaniel Louvard
Mar 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Verónica RodillaLluís Espinosa

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Citations

Dec 8, 2011·Molecular & Cellular Proteomics : MCP·Matthew V MyersDaniel C Liebler
Mar 20, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Derek P SimonGary D Hammer
Aug 7, 2012·The Journal of Clinical Investigation·Huanhuan Joyce ChenSteven Lipkin
Jul 19, 2013·The Journal of Clinical Investigation·Mi-Hwa KimHo Jin You
Apr 6, 2011·Future Oncology·Esther BridgesAdrian Harris
Apr 26, 2014·World Journal of Surgery·Chitra SubramanianMark Cohen
Nov 30, 2012·Annual Review of Physiology·Taeko K Noah, Noah F Shroyer
Oct 8, 2011·Current Colorectal Cancer Reports·Avedis Kazanjian, Noah F Shroyer
Jun 22, 2011·Gastroenterology·Marc VooijsRaphael Kopan
Oct 17, 2018·Oncotarget·David DunkinStephanie Dahan
Dec 19, 2017·Oncology Letters·Magdalena SzaryńskaZbigniew Kmieć
Sep 2, 2016·Journal of Cellular Biochemistry·Leonard H Augenlicht
Jun 24, 2017·Cell Communication and Signaling : CCS·Shaiya C RobinsonJuliet M Daniel
Mar 7, 2021·Cancers·Dorota AnusewiczAndrzej K Bednarek

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