ArticleOncogene2023
The platelet pannexin 1-IL-1β axis orchestrates pancreatic ductal adenocarcinoma invasion and metastasis.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- An immune responsive tumor microenvironment imprints into PBMCs and predicts outcome in advanced pancreatic cancer: lessons from the PREDICT trial.Molecular cancer · 2025Trial
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Panx1 and drug discovery: from non-specific inhibitors to tailored drug compounds.Cell and tissue research · 2026Review
- Defensin-Rich Platelets Drive Pro-Tumorigenic Programs in Pancreatic Adenocarcinoma.International journal of molecular sciences · 2025Article
- Exploring the potential mechanisms of Da ChaiHu decoction against pancreatic cancer based on network pharmacology prediction and molecular docking approach.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Innate Immunity and Platelets: Unveiling Their Role in Chronic Pancreatitis and Pancreatic Cancer.Cancers · 2025Review
- Signaling networks in cancer stromal senescent cells establish malignant microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pannexin channels in inflammation and tumorigenesis.Frontiers in cell and developmental biology · 2025Review
- Pannexin1 channels in the liver: an open enemy.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We aimed to investigate the protumor mechanisms of platelets in pancreatic ductal adenocarcinoma (PDAC). Serum samples were collected from 656 PDAC patients and 3105 healthy people, and a Panx1 knockout tumor model and an adoptive platelet transfusion mouse model were established. We showed that the blood platelet counts were not significantly different between stage III/IV and stage I/II patients, while the number of the CD41+/CD62P+ platelets was significantly elevated in stage III/IV patients, indicating that CD41+/CD62P+ platelets are associated with a poor prognosis. Further analysis showed that a high level of CD41+/CD62P+ platelets was significantly correlated with microvascular invasion (P = 0.002), advanced 8th edition AJCC stage (P < 0.001), and a high CA19-9 level (P = 0.027) and independently predicted a poor prognosis for resectable I/II PDAC. Furthermore, we found significantly higher Panx1 expression in CD41+/CD62P+ platelets than in CD41+/CD62P- platelets in PDAC patients. Mechanistically, Panx1 was able to enhance IL-1β secretion in CD41+/CD62P+ platelets by phosphorylating p38 MAPK and consequently promoted the invasion and metastasis of PDAC cells. Finally, we synthesized a novel compound named PC63435 by the ligation of carbenoxolone (a Panx1 inhibitor) and PSGL-1 (a CD62P ligand). PC63435 specifically bound to CD41+/CD62P+ platelets, then blocked the Panx1/IL-1β pathway and reduced the proportion of CD41+/CD62P+ platelets, which suppressed PDAC tumor invasion and metastasis in vivo. These results demonstrated that the Panx1/IL-1β axis in CD41+/CD62P+ platelets enhanced PDAC cell malignancy and that this axis may be a promising target for PDAC therapy.
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