ReferenceID 4875

Castanospermine suppresses CD44 ectodomain cleavage as revealed by transmembrane bioluminescent sensors

J Cell Sci

Cluster of differentiation 44 (CD44) is a single-pass transmembrane glycoprotein that is a widely distributed cell-surface adhesion molecule. CD44 undergoes ectodomain cleavage by membrane-associated metalloproteinases i

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Reference Id
4875
Evidence Id
21465
Core Evidence Id
21465
Source Reference Id
2993
Herb2 Reference Id
HBREF003790
Subject Paper Key
HBIN019897_35194645
Pubmed Id
35194645
Doi
10.1242/jcs.259314
Paper Title
Castanospermine suppresses CD44 ectodomain cleavage as revealed by transmembrane bioluminescent sensors
Paper Abstract
Cluster of differentiation 44 (CD44) is a single-pass transmembrane glycoprotein that is a widely distributed cell-surface adhesion molecule. CD44 undergoes ectodomain cleavage by membrane-associated metalloproteinases in breast cancer cells. Cleavage plays a critical role in cancer cell migration by mediating the interaction between CD44 and the extracellular matrix. To explore inhibitors of CD44 ectodomain cleavage, we developed two bioluminescent sensors for the detection of CD44 ectodomain cleavage. The sensors were designed as two-transmembrane proteins with split-luciferase fragments, one of which was cyclized by protein trans-splicing of a DnaE intein. These two sensors emit light by the cyclization or the spontaneous complementation of the luciferase fragments. The luminescence intensities decreased upon cleavage of the ectodomain in breast cancer cells. The sensors revealed that castanospermine, an α-glucosidase inhibitor, suppressed the ectodomain cleavage of endogenous CD44 in breast cancer cells. Castanospermine also inhibited breast cancer cell invasion. Thus, the sensors are beneficial tools for evaluating the effects of different inhibitors.
Journal
J Cell Sci
Publish Year
2022
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Cancer; Breast Cancer
Paper Title Cn
Paper Title En
Castanospermine suppresses CD44 ectodomain cleavage as revealed by transmembrane bioluminescent sensors
Bilingual Status
semi_complete