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

Abstract

Introduction: Pancreatic 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.

Methods: Stably 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.

Results: CHRDL1 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.

Discussion: CHRDL1 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.

Keywords: BMP4/SMAD; CHRDL1; invasion; migration; pancreatic cancer.