Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis

Jackstadt, René; Hooff, Sander R. van; Leach, Joshua D.G.; Cortés-Lavaud, Xabier; Lohuis, Jeroen; Ridgway, Rachel A.; Wouters, Valérie M.; Roper, Jatin; Kendall, Timothy J.; Roxburgh, Campbell S.D.; Horgan, Paul G.; Nixon, Colin; Nourse, Craig; Gunzer, Matthias; Clark, William; Hedley, Ann; Yılmaz, Ömer; Rashid, Mamunur; Bailey, Peter J.; Biankin, Andrew V.; Campbell, Andrew D.; Adams, David J.; Barry, Simon T.; Steele, Colin W.; Medema, Jan Paul; Sansom, Owen J.

doi:10.1016/j.ccell.2019.08.003

articleCancer CellSep 1, 2019HYBRID OA

Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis

RJRené Jackstadt SRSander R. van Hooff JDJoshua D.G. Leach XCXabier Cortés-Lavaud JLJeroen Lohuis

Cancer Research UK Scotland Institute · Amsterdam UMC Location University of Amsterdam · +11 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

-driven serrated cancer. Transcriptional profiling reveals that epithelial NOTCH1 signaling creates a tumor microenvironment (TME) reminiscent of poorly prognostic human CRC subtypes (CMS4 and CRIS-B), and drives metastasis through transforming growth factor (TGF) β-dependent neutrophil recruitment. Importantly, inhibition of this recruitment with clinically relevant therapeutic agents blocks metastasis. We propose that NOTCH1 signaling is key to CRC progression and should be exploited clinically.

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Topics & keywords

Topics

Keywords

Colorectal cancer
Notch signaling pathway
Metastasis
Cancer research
Cancer
Tumor microenvironment
Signal transduction
Medicine

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