Related Experiment Video

Updated: May 15, 2025

Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study
11:10

Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study

Published on: June 29, 2016

14.0K

The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells

Hong Phuong Nguyen1, Enze Liu2, Anh Quynh Le1

  • 1Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.

Molecular Therapy. Oncology
|April 9, 2025
PubMed

Insights

The oligosaccharyltransferase (OST) complex is a new target for multiple myeloma (MM). Inhibiting OST combined with bortezomib effectively eliminated MM cells, offering hope for relapsed patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Multiple myeloma (MM) is an incurable plasma cell malignancy with significant clinical impact.
  • Current treatments face challenges, necessitating novel therapeutic strategies.
  • Identifying new molecular targets is crucial for improving MM patient outcomes.

Purpose of the Study:

  • To investigate the oligosaccharyltransferase (OST) complex as a potential therapeutic target in multiple myeloma.
  • To evaluate the efficacy of OST complex disruption, alone and in combination with bortezomib, in MM.

Main Methods:

  • Expression analysis of the OST complex in MM patient samples.
  • In vitro and in vivo studies assessing the effects of OST complex inhibition on MM cell growth, cell cycle, and apoptosis.
  • Combination therapy studies with bortezomib.
  • Mechanistic studies to elucidate the downstream effects of OST inhibition on MM signaling pathways.

Main Results:

  • Elevated OST complex expression correlates with relapsed, high-risk MM and poor prognosis.
  • Disruption of the OST complex inhibited MM cell proliferation, induced cell-cycle arrest, and promoted apoptosis.
  • Combined OST inhibition and bortezomib synergistically eradicated MM cells in vitro and in vivo.
  • OST complex inhibition downregulated key MM pathways (mTORC1, glycolysis, MYC, cell cycle) and enhanced TRAIL-mediated apoptosis.
  • MYC translation was significantly suppressed by OST complex inhibition.

Conclusions:

  • The OST complex represents a novel and promising therapeutic target for multiple myeloma.
  • Combined inhibition of the OST complex and bortezomib demonstrates significant therapeutic potential, particularly for relapsed MM.
  • Targeting the OST complex offers a strategy to overcome bortezomib resistance by modulating critical MM-associated pathways.
Keywords:
MT: Regular IssueMYC translationN-glycosylationapoptosisbortezomib resistancecell-cycle arrestmTOCR1 pathwaymultiple myelomaoligosaccharyltransferase complexpost-translational modificationrelapsed/refractory myelomaxenograft model

More Related Videos

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

12.0K
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

8.6K

Related Concept Videos

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...
2.7K
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.2K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.3K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Proteoglycans01:05

Proteoglycans

Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.8K