ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1633464
Chorordin-like 1 Inhibits Pancreatic Cancer Cell Migration and Invasion: Involvement of the BMP4/SMAD Pathway
Provisionally accepted
- First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Pancreatic cancer represents one of the most aggressive malignancies, with a mere 6% five-year survival rate. CHRDL1, regarded as an antagonist of BMP4, has demonstrated tumor-suppressive effects in cancers such as breast and gastric carcinomas. However, its role in pancreatic cancer remains unclear. Lentivirusmediated CHRDL1 overexpression was employed to establish stably transfected pancreatic cancer cell lines (PANC-1 and SW1990), which were then used to assess the effects of CHRDL1 on cell proliferation, migration, and adhesion. Recombinant BMP4 treatment was applied to validate CHRDL1's antagonistic role against BMP4.In our study, we found CHRDL1 was downregulated in pancreatic cancer and associated with poor prognosis, as confirmed by TCGA database, immunohistochemistry, and RT-qPCR in both cell lines and patient tissues. CHRDL1 overexpression inhibited pancreatic cancer cell migration and adhesion but had no significant effect on proliferation. Mechanistically, CHRDL1 overexpression reduced SMAD1/5/9 phosphorylation and RUNX2 expression. CHRDL1 counteracted the pro-migratory and pro-adhesive effects of recombinant BMP4, confirming its role as a BMP4 antagonist. In vivo experiments demonstrated that CHRDL1-overexpressing cells generated fewer pulmonary metastases. Our study reveals that CHRDL1 exerts tumor-suppressive effects in pancreatic cancer by inhibiting the BMP4/SMAD pathway, thereby attenuating migration, invasion, and metastasis.
Keywords: Pancreatic Cancer, Chrdl1, BMP4/SMAD, Migration, invasion
Received: 22 May 2025; Accepted: 16 Jul 2025.
Copyright: © 2025 Li, Zhong, Song, Wang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zheng Jiang, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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