ArticleOncogene2024
GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Deguelin inhibits perineural invasion in esophageal squamous cell carcinoma via targeting BDNF/TrkB axis.Cancer biology & therapy · 2026Article
- Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.Molecular biomedicine · 2026Review
- Transmembrane mucin 21 drives lung adenocarcinoma growth by suppressing retinoic acid receptor β signaling.Journal of thoracic disease · 2026Article
- Integrins as key regulators in tumor perineural invasion: mechanisms and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Pathophysiology, assessment, and treatment of pain in patients with pancreatic ductal adenocarcinoma.Journal of gastroenterology · 2026Article
- Neural-tumor crosstalk and molecular targeting: mechanisms and therapeutic implications in cancer neuroscience.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Review
- Neural-immune-cancer crosstalk in pancreatic cancer: mechanisms and clinical translation.Frontiers in cell and developmental biology · 2026Review
- Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.International journal of medical sciences · 2026Review
- MUC21 is downregulated in oral squamous cell carcinoma and associated with poor prognosis.Frontiers in oncology · 2026Article
- Single-Cell Sequencing Unravels Pancreatic Cancer: Novel Technologies Reveal Novel Aspects of Cellular Heterogeneity and Inform Therapeutic Strategies.Biomedicines · 2025Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Cancer and neurotransmitter receptors.Chinese medical journal · 2025Review
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Significance and mechanisms of perineural invasion in malignant tumors.Frontiers in oncology · 2025Review
- ATIC Knockdown Reduces B7-H3 Expression and Oncogenic Signaling in Upper Tract Urothelial Carcinoma Cells.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.
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Registered trials
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