Chorordin-like 1 inhibits pancreatic cancer cell migration and invasion: involvement of the BMP4/SMAD pathway

Chorordin-like 1 inhibits pancreatic cancer cell migration and invasion: involvement of the BMP4/SMAD pathway

IntroductionPancreatic cancer is a highly aggressive malignancy with a 6% five-year survival rate. CHRDL1, a BMP4 antagonist, has tumor-suppressive effects in breast and gastric cancers, but its role in pancreatic cancer is unclear. This study explores CHRDL1’s function and mechanism in pancreatic c...

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Bibliographic Details
Main Authors: Wei Li, Yalan Zhong, Yuqiao Song, Hongmei Wang, Zheng Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
Subjects:
pancreatic cancer
CHRDL1
BMP4/SMAD
migration
invasion
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1633464/full
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Summary:IntroductionPancreatic cancer is a highly aggressive malignancy with a 6% five-year survival rate. CHRDL1, a BMP4 antagonist, has tumor-suppressive effects in breast and gastric cancers, but its role in pancreatic cancer is unclear. This study explores CHRDL1’s function and mechanism in pancreatic cancer.MethodsStably transfected pancreatic cancer cell lines (PANC-1, SW1990) with lentivirus-mediated CHRDL1 overexpression were established to assess effects on cell proliferation, migration, and adhesion. Recombinant BMP4 treatment validated CHRDL1’s antagonism. Additionally, the TCGA database, immunohistochemistry, and RT-qPCR in both cell lines and patient tissues confirmed CHRDL1 expression. In vivo experiments were also conducted to observe the effect of CHRDL1 overexpression on pulmonary metastases.ResultsCHRDL1 was downregulated in pancreatic cancer, correlating with poor prognosis. Overexpression inhibited cell migration and adhesion (without affecting proliferation), reduced SMAD1/5/9 phosphorylation and RUNX2 expression, and counteracted BMP4-induced malignant behaviors.DiscussionCHRDL1 exerts tumor-suppressive effects in pancreatic cancer by inhibiting the BMP4/SMAD pathway, reducing migration, invasion, and metastasis. These findings clarify CHRDL1’s role, enhance understanding of pancreatic cancer mechanisms, and may offer diagnostic and therapeutic targets.
ISSN:2234-943X

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