ArticleThe Journal of clinical investigation2022
KRAS mutant-driven SUMOylation controls extracellular vesicle transmission to trigger lymphangiogenesis 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 45 papers.
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Who cites it
45 citing papers in PubMed, 58 citations in OpenAlex.
- MVB Maturation Responsive to KRASJournal of extracellular vesicles · 2026Article
- Extracellular vesicle biomarkers in pancreatic ductal adenocarcinoma: from bulk detection to single-extracellular vesicle profiling and endoscopic liquid biopsy.Journal of gastroenterology · 2026Review
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Pancreatic Lymphatics in Health and Disease: Evolution, Embryology, and Neural Control.Lymphatics · 2026Article
- Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway.Cell death & disease · 2026Article
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- IL1RAJournal of clinical and translational hepatology · 2025Article
- Review
- DeSUMOylation of RBMX regulates exosomal sorting of cargo to promote renal tubulointerstitial fibrosis in diabetic kidney disease.Journal of advanced research · 2025Article
- Extracellular vesicle-mediated transmission of circPDLIM5 promotes lymphatic metastasis in prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- CircERC1 facilitates chemoresistance through inhibiting pyroptosis and remodeling extracellular matrix in pancreatic cancer.Molecular cancer · 2025Article
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- SPHK1 Promotes Pancreatic Cancer Lymphangiogenesis Through the Activation of ERK in LECs.Molecular biotechnology · 2025Article
- SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression.Oncogene · 2025Article
- Tumor-derived exosomal CCT6A serves as a matchmaker introducing chemokines to tumor-associated macrophages in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Article
- STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis.Cell death & disease · 2025Article
- Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.ACS nano · 2025Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC) and predicts poor prognosis for patients. The KRASG12D mutation confers an aggressive PDAC phenotype that is susceptible to lymphatic dissemination. However, the regulatory mechanism underlying KRASG12D mutation-driven LN metastasis in PDAC remains unclear. Herein, we found that PDAC with the KRASG12D mutation (KRASG12D PDAC) sustained extracellular vesicle-mediated (EV-mediated) transmission of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in a SUMOylation-dependent manner and promoted lymphangiogenesis and LN metastasis in vitro and in vivo. Mechanistically, hnRNPA1 bound with SUMO2 at the lysine 113 residue via KRASG12D-induced hyperactivation of SUMOylation, which enabled its interaction with TSG101 to enhance hnRNPA1 packaging and transmission via EVs. Subsequently, SUMOylation induced EV-packaged-hnRNPA1 anchoring to the adenylate- and uridylate-rich elements of PROX1 in lymphatic endothelial cells, thus stabilizing PROX1 mRNA. Importantly, impeding SUMOylation of EV-packaged hnRNPA1 dramatically inhibited LN metastasis of KRASG12D PDAC in a genetically engineered KrasG12D/+ Trp53R172H/+ Pdx-1-Cre (KPC) mouse model. Our findings highlight the mechanism by which KRAS mutant-driven SUMOylation triggers EV-packaged hnRNPA1 transmission to promote lymphangiogenesis and LN metastasis, shedding light on the potential application of hnRNPA1 as a therapeutic target in patients with KRASG12D PDAC.
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