ArticleThe Journal of clinical investigation2022
KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Article
- hnRNPA1-SF3B3 interaction drives radioresistance in oral squamous cell carcinoma by modulating MARF1 alternative splicing isoforms.Journal of experimental & clinical cancer research : CR · 2026Article
- Exosome applications for the diagnosis and treatment of pancreatic ductal adenocarcinoma: An update (Review).Oncology reports · 2025Review
- The Past, Present, and Future of Biomarkers for the Early Diagnosis of Pancreatic Cancer.Biomedicines · 2024Review
- Regulation of HNRNP family by post-translational modifications in cancer.Cell death discovery · 2024Review
- Extracellular vesicle and lipoprotein diagnostics (ExoLP-Dx) with membrane sensor: A robust microfluidic platform to overcome heterogeneity.Biomicrofluidics · 2024Article
- Extracellular Signal-Regulated Kinase Inhibitor SCH772984 Augments the Anti-Cancer Effects of Gemcitabine in Nanoparticle Form in Pancreatic Cancer Models.International journal of molecular and cellular medicine · 2024Article
- The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.Cell death & disease · 2023Article
- Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma.Cancer research · 2023Article
- Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect.Cancers · 2023Review
- Diagnostic and Prognostic Role of Extracellular Vesicles in Pancreatic Cancer: Current Evidence and Future Perspectives.International journal of molecular sciences · 2023Review
- The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth.BioMed research international · 2022Article
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Authors and funding
2 authors at 2 institutions in 3 countries.
Funding
Abstract
Kirsten rat sarcoma virus (KRAS) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRASG12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI, Luo, Li, et al. explored the relationship between the presence of the KRASG12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRASG12D induced SUMOylation of heterogenous nuclear ribonucleoprotein A1 (hnRNPA1) via SAE1 and SUMO2 activation. SUMOylated hnRNPA1 was loaded into extracellular vesicles (EVs) and internalized by human endothelial lymphatic cells (HLEC). Further, SUMOylated hnRNPA1 promoted lymphangiogenesis and LN metastasis by stabilizing prospero homeodomain protein 1 (PROX1) mRNA. These data provide mechanistic insight into cancer lymphangiogenesis with the potential for developing biomarkers and RAS pathway therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.