ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.Cancer immunology, immunotherapy : CII · 2024Trial
- Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-rasGastroenterology · 2026Article
- MUC16 promotes endometrial cancer progression and modulates sensitivity to lapatinib through the ESR1/PI3K/AKT axis.Translational oncology · 2026Article
- Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?Cancer medicine · 2026Review
- From Pyroptosis Heterogeneity to an Interpretable Prognostic Signature for Risk Stratification and Therapy Insights in Pancreatic Adenocarcinoma.Biomedicines · 2026Article
- Deletion of Core 1 β3GalT-specific molecular chaperone (Cosmc) in murine intestinal epithelia leads to major alterations in glycocalyx and tumorigenesis.The Journal of biological chemistry · 2026Article
- Spatially-resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- In Search of Ideal Solutions for Cancer Diagnosis: From Conventional Methods to Protein Biomarkers in Liquid Biopsy.Proteomes · 2025Review
- Mucin-Targeted Antibodies for Ovarian Cancer.Seminars in nuclear medicine · 2025Review
- Early-Stage Pancreatic Cancer Diagnosis: Serum Biomarkers and the Potential for Aptamer-Based Biosensors.Molecules (Basel, Switzerland) · 2025Review
- Redefining phenotypic intratumor heterogeneity of pancreatic ductal adenocarcinoma: a bottom-up approach.The Journal of pathology · 2025Article
- Humanized Anti-MUC16 Antibody-Conjugated Contrast Agents for Magnetic Resonance Imaging of Pancreatic Cancer.Cancers · 2025Article
- Tumor-associated Tn and STn antigens: from molecular mechanism to precision diagnosis and treatment.Frontiers in immunology · 2025Review
- Machine learning and gene network integration reveal prognostic subnetworks and biomarkers in pancreatic cancer.Computational and structural biotechnology journal · 2025Article
- Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer.Molecular therapy. Oncology · 2024Article
- The glycogene alterations and potential effects in esophageal squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- A signal-diffusion-based unsupervised contrastive representation learning for spatial transcriptomics analysis.Bioinformatics (Oxford, England) · 2024Article
- Novel progressive deep learning algorithm for uncovering multiple single nucleotide polymorphism interactions to predict paclitaxel clearance in patients with nonsmall cell lung cancer.Cancer innovation · 2024Article
- GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase.Oncogene · 2024Article
- Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6.Molecular cancer therapeutics · 2024Article
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Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
Abstract
Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3β oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.
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