Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells.
Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer, and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori, and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human alpha-L-fucosidase 2 (FUCA2) is secreted only under coculture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer- and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.
Liu
Ta-Wei
TW
Institute of Biological Chemistry and The Genomics Research Center, Institute of Chemistry, and Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, Nan-Kang, Taipei 11529, Taiwan.
Ho
Ching-Wen
CW
Huang
Hsin-Hung
HH
Chang
Sue-Ming
SM
Popat
Shide D
SD
Wang
Yi-Ting
YT
Wu
Ming-Shiang
MS
Chen
Yu-Ju
YJ
Lin
Chun-Hung
CH
D000230:Adenocarcinoma / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D005643:Fucose / Q000737:chemistry / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D016256:Lewis X Antigen / Q000378:metabolism; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D015394:Molecular Structure; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D013274:Stomach Neoplasms / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D013379:Substrate Specificity; D005644:alpha-L-Fucosidase / Q000235:genetics / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007527:Isoenzymes; D016256:Lewis X Antigen; C080866:cagA protein, Helicobacter pylori; D005643:Fucose; D005644:alpha-L-Fucosidase