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

Fingerprint

Colorectal Neoplasms
Glycosphingolipids
Tissue
Galactosyltransferases
Ceramides
HCT116 Cells
Biomarkers
Therapeutics
Metabolites
Tumors
Transducers
Assays
Cells
Enzyme-Linked Immunosorbent Assay
UDPgalactose-glucosylceramide galactosyltransferase
triaosylceramide 1,4-galactosyltransferase
Staining and Labeling
Gene Expression
Polymerase Chain Reaction
Proteins

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

Cite this

Lactosylceramide synthase β-1,4-GalT-V : A novel target for the diagnosis and therapy of human colorectal cancer. / Chatterjee, Subroto B; Hou, Jennifer; Ratnam Bandaru, Veera Venkata; Pezhouh, Maryam Kherad; Syed Rifat Mannan, Abul Ala; Sharma, Rajni.

In: Biochemical and Biophysical Research Communications, 01.01.2018.

Research output: Contribution to journalArticle

Chatterjee, Subroto B ; Hou, Jennifer ; Ratnam Bandaru, Veera Venkata ; Pezhouh, Maryam Kherad ; Syed Rifat Mannan, Abul Ala ; Sharma, Rajni. / Lactosylceramide synthase β-1,4-GalT-V : A novel target for the diagnosis and therapy of human colorectal cancer. In: Biochemical and Biophysical Research Communications. 2018.
@article{4fad041560454db391544967890bba29,
title = "Lactosylceramide synthase β-1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer",
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.",
keywords = "Biomarker, Colorectal cancer, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, Galactosyltransferase, Lactosylceramide, UDP-Galactose: β-1,4-galactosyltransferase V",
author = "Chatterjee, {Subroto B} and Jennifer Hou and {Ratnam Bandaru}, {Veera Venkata} and Pezhouh, {Maryam Kherad} and {Syed Rifat Mannan}, {Abul Ala} and Rajni Sharma",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbrc.2018.11.149",
language = "English (US)",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Lactosylceramide synthase β-1,4-GalT-V

T2 - A novel target for the diagnosis and therapy of human colorectal cancer

AU - Chatterjee, Subroto B

AU - Hou, Jennifer

AU - Ratnam Bandaru, Veera Venkata

AU - Pezhouh, Maryam Kherad

AU - Syed Rifat Mannan, Abul Ala

AU - Sharma, Rajni

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Colorectal cancer

KW - D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol

KW - Galactosyltransferase

KW - Lactosylceramide

KW - UDP-Galactose: β-1,4-galactosyltransferase V

UR - http://www.scopus.com/inward/record.url?scp=85057274564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057274564&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2018.11.149

DO - 10.1016/j.bbrc.2018.11.149

M3 - Article

C2 - 30502090

AN - SCOPUS:85057274564

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -