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Lactosylceramide synthase β-1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Jan 08; Vol. 508 (2), pp. 380-386. Date of Electronic Publication: 2018 Nov 28. - Publication Year :
- 2019
-
Abstract
- Little is known about an oncogenic signal transducer β-1,4-galactosyltransferase-V (β-1,4-GalT-V), in human colorectal cancer. Using quantitative RT-PCR, immunohistochemical staining and ELISA assays, we determined that β-1,4-GalT-V gene/protein expression is specifically increased in human colorectal cancer (CRC) tumors, compared to visibly normal tissue. Furthermore, we observed a marked increase in its enzymatic activity, and its product lactosylceramide. Moreover, we found increased dihydrosphingolipid metabolites, in particular dihydrosphingomyelin in cancer tissue compared to normal. Further, inhibition of glycosphingolipid synthesis by the synthetic ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), concurrently inhibited colorectal cancer cell (HCT-116) proliferation, as well as β-1,4-GalT-V mass and several glycosphingolipid levels. We conclude that β-1,4-GalT-V may serve as a diagnostic and therapeutic biomarker for the progression of human colorectal cancer, and consequently, inhibition of GSL synthesis may be a novel approach for the treatment of this life-threatening disease.<br /> (Copyright © 2018. Published by Elsevier Inc.)
- Subjects :
- Biomarkers, Tumor antagonists & inhibitors
Cell Proliferation drug effects
Colorectal Neoplasms diagnosis
Colorectal Neoplasms drug therapy
Dose-Response Relationship, Drug
Enzyme Inhibitors administration & dosage
Enzyme Inhibitors pharmacology
Galactosyltransferases antagonists & inhibitors
HCT116 Cells
Humans
Immunohistochemistry
Lactosylceramides biosynthesis
Morpholines administration & dosage
Morpholines pharmacology
Signal Transduction drug effects
Sphingolipids biosynthesis
Up-Regulation
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Colorectal Neoplasms enzymology
Galactosyltransferases genetics
Galactosyltransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 508
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30502090
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.11.149