Cancer-induced inflammation and inflammation-induced cancer in colon: a role for S1P lyase

Oncogene
Anja SchwiebsHeinfried H Radeke

Abstract

A role of sphingolipids for inflammatory bowel disease and cancer is evident. However, the relative and separate contribution of sphingolipid deterioration in inflammation versus carcinogenesis for the pathophysiology of colitis-associated colon cancer (CAC) was unknown and therefore examined in this study. We performed isogenic bone marrow transplantation of inducible sphingosine-1-phosphate (S1P) lyase knockout mice to specifically modulate sphingolipids and associated genes and proteins in a compartment-specific way in a DSS/AOM mediated CAC model. 3D organoid cultures were used in vitro. S1P lyase (SGPL1) knockout in either immune cells or tissue, caused local sphingolipid accumulation leading to a dichotomic development of CAC: Immune cell SGPL1 knockout (I-SGPL-/-) augmented massive immune cell infiltration initiating colitis with lesions and calprotectin increase. Pathological crypt remodeling plus extracellular S1P-signaling caused delayed tumor formation characterized by S1P receptor 1, STAT3 mRNA increase, as well as programmed cell death ligand 1 expression, accompanied by a putatively counter regulatory STAT1S727 phosphorylation. In contrast, tissue SGPL1 knockout (T-SGPL-/-) provoked immediate occurrence of epithel...Continue Reading

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Citations

Sep 25, 2020·Lipids·Wajiha Farha Faqar-Uz-ZamanAnja Schwiebs
Sep 25, 2020·FEBS Letters·Nigel J Pyne, Susan Pyne
Nov 30, 2019·International Journal of Molecular Sciences·Brigitta KisCorina Danciu
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Petra Grbčić, Mirela Sedić
Dec 6, 2019·International Journal of Molecular Sciences·Miroslav MachalaJan Vondráček
Dec 7, 2019·Cancer Cell International·Peng WangXun Qi
Dec 16, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Xianwang WangYingying Lu
Feb 5, 2021·International Journal of Molecular Sciences·Kyong-Oh ShinYong-Moon Lee
Jun 3, 2021·International Journal of Molecular Sciences·Anja SchwiebsHeinfried H Radeke
Jul 11, 2021·Cellular Signalling·Real Sumayya Abdul SattarSundeep Singh Saluja

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Methods Mentioned

BETA
ELISA
Assay
PCR

Software Mentioned

GraphPad Prism

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