Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis.
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ABSTRACT:
SUBMITTER: Jackstadt R
PROVIDER: S-EPMC6853173 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis.
Jackstadt Rene R van Hooff Sander R SR Leach Joshua D JD Cortes-Lavaud Xabier X Lohuis Jeroen O JO Ridgway Rachel A RA Wouters Valérie M VM Roper Jatin J Kendall Timothy J TJ Roxburgh Campbell S CS Horgan Paul G PG Nixon Colin C Nourse Craig C Gunzer Matthias M Clark William W Hedley Ann A Yilmaz Omer H OH Rashid Mamunur M Bailey Peter P Biankin Andrew V AV Campbell Andrew D AD Adams David J DJ Barry Simon T ST Steele Colin W CW Medema Jan Paul JP Sansom Owen J OJ
Cancer cell 20190901 3
The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation of NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) in Kras<sup>G12D</sup>-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), an ...[more]
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