title: Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation.
abstract: Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools.
authors: Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt.
authors: Haitham A
authors: HA
authors: Badr
authors: Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
authors: Dina M M
authors: DM
authors: AlSadek
authors: Department of Biomedical Engineering and Translational Tissue Engineering Center, The Johns Hopkins University, 400 North Broadway Street, Baltimore, MD 21231, USA.
authors: Mohit P
authors: MP
authors: Mathew
authors: Department of Biomedical Engineering, Florida International University, 10555 West Flagler Street, Miami, FL 33174, USA.
authors: Chen-Zhong
authors: CZ
authors: Li
authors: Institute of General Genetics and Cytology, Al-Farabi Ave, 93, Almaty 050060, Kazakhstan.
authors: Leyla B
authors: LB
authors: Djansugurova
authors: Department of Biomedical Engineering and Translational Tissue Engineering Center, The Johns Hopkins University, 400 North Broadway Street, Baltimore, MD 21231, USA. Electronic address: kyarema1@jhu.edu.
authors: Kevin J
authors: KJ
authors: Yarema
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine and Institute of Marine and Environmental Technology, 701 East Pratt Street, Baltimore, MD 21202, USA. Electronic address: hfzahmed86@gmail.com.
authors: Hafiz
authors: H
authors: Ahmed
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D002470:Cell Survival; D066246:ErbB Receptors / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000378:metabolism; D009005:Monosaccharides / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009711:Nucleotides / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism
chemical_list: D006001:Glycoconjugates; D037102:Lectins; D009005:Monosaccharides; D018396:Mucin-1; C078888:N-(O-acetyl)glycoloylneuraminic acid; D009711:Nucleotides; D012794:Sialic Acids; D000255:Adenosine Triphosphate; D012799:Sialyltransferases; C029156:N-acetyllactosaminide alpha-2,3-sialyltransferase; D066246:ErbB Receptors; D019158:N-Acetylneuraminic Acid
keywords: Cancer cell; Lectins; Metabolism; Nutrient deprivation; Sialic acid; Surface sensing