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Lactosylceramide synthase β-1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer.

Biochem. Biophys. Res. Commun.2019 Jan 08;508(2):380-386. Epub 2018 Nov 28
Subroto B Chatterjee 1 , Jennifer Hou 2 , Veera Venkata Ratnam Bandaru 3 , Maryam Kherad Pezhouh 4 , Abul Ala Syed Rifat Mannan 5 , Rajni Sharma 5
Subroto B Chatterjee 1 , Jennifer Hou 2 , Veera Venkata Ratnam Bandaru 3 , Maryam Kherad Pezhouh 4 , Abul Ala Syed Rifat Mannan 5 , Rajni Sharma 5
+ et al

[No authors listed]

Author information
  • 1 Pediatrics and Medicine Department, Johns Hopkins University Hospital, Blalock 1383, Baltimore, MD, 21287, USA. Electronic address: schatte2@jhmi.edu.
  • 2 Pediatrics and Medicine Department, Johns Hopkins University Hospital, Blalock 1383, Baltimore, MD, 21287, USA.
  • 3 Neurology Department, JHU Hospital, Baltimore, MD, 21287, USA.
  • 4 Pathology Department, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
  • 5 Pathology Department, Division of Surgical Pathology, SOM, JHU, Baltimore, MD, 21287, USA.

摘要

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.

KEYWORDS: Biomarker, Colorectal cancer, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, Galactosyltransferase, Lactosylceramide, UDP-Galactose: β-1,4-galactosyltransferase V

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