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

Subroto B. Chatterjee, Jennifer Hou, Veera Venkata Ratnam Bandaru, Maryam Kherad Pezhouh, Abul Ala Syed Rifat Mannan, Rajni Sharma

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBiochemical and Biophysical Research Communications
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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