O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on

Related Experiment Video

Updated: Dec 14, 2025

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

2.9K

Yuliang Jiang1,2, Tao Wen2, Rui Yan2

  • 1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 22, 2020
PubMed

Insights

Truncated O-glycans like Tn and Sialyl-Tn (STn) on tumor cells reduce sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by impairing death receptor stability. Restoring normal O-glycans increases TRAIL sensitivity, offering survival advantages.

Area of Science:

  • Cell Biology
  • Glycobiology
  • Cancer Research

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis via death receptors (DR4/DR5).
  • Cancer cells often display truncated O-glycans (Tn, Sialyl-Tn/STn), but their role in TRAIL sensitivity is unclear.
  • O-glycan biosynthesis is regulated by Cosmc, which aids T-synthase folding for extended O-glycan structures.

Purpose of the Study:

  • To investigate the role of truncated O-glycans (Tn/STn) in TRAIL-induced apoptosis.
  • To elucidate the molecular mechanisms by which O-glycans influence cancer cell sensitivity to TRAIL.
  • To determine if restoring normal O-glycans impacts TRAIL sensitivity.

Main Methods:

  • Utilized tumor cell lines with Cosmc mutations expressing Tn/STn antigens.
  • Transfected these cells with wild-type Cosmc to restore normal O-glycan expression.
  • Assessed changes in sensitivity to TRAIL treatment.
  • Analyzed the impact of O-glycans on DR4 and DR5 receptor homo-oligomerization and stability.

Main Results:

  • Tumor cells expressing Tn/STn antigens showed reduced sensitivity to TRAIL.
  • Restoration of normal O-glycans via wild-type Cosmc transfection increased TRAIL sensitivity.
  • Tn/STn antigens were found to impair the homo-oligomerization and stability of DR4 and DR5 receptors.

Conclusions:

  • Cell surface O-glycan structures, specifically Tn/STn antigens, modulate sensitivity to TRAIL-induced apoptosis.
  • Truncated O-glycans (Tn/STn) may confer a survival advantage to tumor cells by reducing DR4/DR5 activity.
  • This study provides the first mechanistic insight into how O-glycans influence apoptotic signaling pathways.
Keywords:
CosmcO-glycosylationSTn antigenTn antigentumor cells

More Related Videos

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.4K
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

9.0K

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.7K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
8.9K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
4.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.9K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
13.5K
Oligosaccharide Assembly01:24

Oligosaccharide Assembly

Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
3.4K