ArticleMolecular cancer research : MCR2022
MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion.
Article in Molecular cancer research : MCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-rasGastroenterology · 2026Article
- Distinct glycosyltransferase expression governs organ-specific survival in pancreatic cancer metastasis.Oncogene · 2026Article
- Safe and Effective Histotripsy Ablation of Human Liver Tumors in a Genetically Modified Porcine Model.Cancers · 2026Article
- Cytotoxic activity and safety characterization of IMV-M™, a MUC16 × DR5 bispecific antibody.Antibody therapeutics · 2026Article
- Revealing the Potential Associations of Mutation-Related Genes with Lymph Node Metastasis in Gallbladder Cancer Through Transcriptome and Exome Sequencing.Biomedicines · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Targeting MUC16 to Reverse Anoikis Resistance: A Promising Strategy for Metastatic Lung Adenocarcinoma Therapy.Journal of Cancer · 2026Article
- Targeting cancer-associated fibroblast-driven LIF/LIFR axis improves the therapeutic efficacy of gemcitabine and nab-paclitaxel in pancreatic cancer.NPJ precision oncology · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- Sugar symphony: glycosylation in cancer metabolism and stemness.Trends in cell biology · 2025Review
- The Role of Antigen Carbohydrate 125 in Modulating Soluble ST2: Prognostic-Related Effects in Acute Heart Failure.Biomolecules · 2025Article
- Development of a predictive model for metachronous liver metastasis in gastric cancer.Frontiers in oncology · 2025Article
- RRM2 promotes liver metastasis of pancreatic cancer by stabilizing YBX1 and activating the TGF-beta pathway.iScience · 2024Article
- Targeting Human Pancreatic Cancer with a Fluorophore-Conjugated Mucin 4 (MUC4) Antibody: Initial Characterization in Orthotopic Cell Line Mouse Models.Journal of clinical medicine · 2024Article
- Hypomethylation-associated ELF3 helps nasopharyngeal carcinoma to escape immune surveillance via MUC16-mediated glycolytic metabolic reprogramming.American journal of physiology. Cell physiology · 2024Article
- RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway.eLife · 2024Article
- MUC16: clinical targets with great potential.Clinical and experimental medicine · 2024Review
- Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer.Journal of translational medicine · 2024Article
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
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Authors and funding
16 authors at 2 institutions in 1 country.
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, as it commonly metastasizes to the liver resulting in an overall poor prognosis. However, the molecular mechanism involved in liver metastasis remains poorly understood. Here, we aimed to identify the MUC16-mediated molecular mechanism of PDAC-liver metastasis. Previous studies demonstrated that MUC16 and its C-terminal (Cter) domain are involved in the aggressiveness of PDAC. In this study, we observed MUC16 and its Cter expression significantly high in human PDAC tissues, PDAC organoids, and metastatic liver tissues, while no expression was observed in normal pancreatic tissues using IHC and immunofluorescence (IFC) analyses. MUC16 knockdown in SW1990 and CD18/HPAF PDAC cells significantly decreased the colony formation, migration, and endothelial/p-selectin binding. In contrast, MUC16-Cter ectopic overexpression showed significantly increased colony formation and motility in MiaPaCa2 pancreatic cancer cells. Interestingly, MUC16 promoted cell survival and colonization in the liver, mimicking an ex vivo environment. Furthermore, MUC16 enhanced liver metastasis in the in vivo mouse model. Our integrated analyses of RNA-sequencing suggested that MUC16 alters Neuropilin-2 (NRP2) and cell adhesion molecules in pancreatic cancer cells. Furthermore, we identified that MUC16 regulated NRP2 via JAK2/STAT1 signaling in PDAC. NRP2 knockdown in MUC16-overexpressed PDAC cells showed significantly decreased cell adhesion and migration. Overall, the findings indicate that MUC16 regulates NRP2 and induces metastasis in PDAC. IMPLICATIONS: This study shows that MUC16 plays a critical role in PDAC liver metastasis by mediating NRP2 regulation by JAK2/STAT1 axis, thereby paving the way for future therapy efforts for metastatic PDAC.
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