2. Academic Validation
  3. The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells

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

  • Mol Ther Oncol. 2025 Mar 8;33(2):200964. doi: 10.1016/j.omton.2025.200964.
Hong Phuong Nguyen 1,  Enze Liu 2,  Anh Quynh Le 1,  Mahesh Lamsal 1,  Jagannath Misra 3,  Sankalp Srivastava 1,  Harikrishnan Hemavathy 1,  Reuben Kapur 1,  Mohammad Abu Zaid 2,  Rafat Abonour 2,  Ji Zhang 1 3,  Ronald C Wek 3,  Brian A Walker 2 4,  Ngoc Tung Tran 1
Affiliations

Affiliations

  • 1 Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • 2 Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology and Oncology, School of Medicine, Indiana University, Indianapolis, IN, USA.
  • 3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • 4 Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University, Indianapolis, IN, USA.
PMID: 40200920 DOI: 10.1016/j.omton.2025.200964
Abstract

Multiple myeloma (MM) is an incurable malignancy characterized by mutated plasma cell clonal expansion in the bone marrow, leading to severe clinical symptoms. Thus, identifying new therapeutic targets for MM is crucial. We identified the oligosaccharyltransferase (OST) complex as a novel vulnerability in MM cells. Elevated expression of this complex is associated with relapsed, high-risk MM, and poor prognosis. Disrupting the OST complex suppressed MM cell growth, induced cell-cycle arrest, and Apoptosis. Combined inhibition with bortezomib synergistically eliminated MM cells in vitro and in vivo, via suppressing genes related to bortezomib-resistant phenotypes. Mechanistically, OST complex disruption downregulated MM pathological pathways (mTORC1 pathway, glycolysis, MYC targets, and cell cycle) and induced TRAIL-mediated Apoptosis. Notably, MYC translation was robustly suppressed upon inhibiting the OST complex. Collectively, the OST complex presents a novel target for MM treatment, and combining its inhibition with bortezomib offers a promising approach for relapsed MM patients.

Keywords

MT: Regular Issue; MYC translation; N-glycosylation; apoptosis; bortezomib resistance; cell-cycle arrest; mTOCR1 pathway; multiple myeloma; oligosaccharyltransferase complex; post-translational modification; relapsed/refractory myeloma; xenograft model.

Figures
Products