Protocadherin 1 (PCDH1) Promotes Pancreatic Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition (EMT) Progression Through the NF-κB Pathway.

[OBJECTIVE] This study investigates the role of the protocadherin-1 (PCDH1) gene in pancreatic cancer metastasis, focusing on its influence on the epithelial-mesenchymal transition (EMT) process and the NF-κB signaling pathway.

[METHODS] Clinical specimens from pancreatic cancer patients were analyzed through bioinformatics to correlate PCDH1 expression with disease staging, pathological grade, metastasis, and prognosis. Cellular experiments using siRNA knockdown and plasmid overexpression were conducted, with assays such as CCK-8, Transwell, and flow cytometry to evaluate cell proliferation, invasion, and apoptosis. Western blot, qRT-PCR, and immunofluorescence assays were used to assess PCDH1 expression and its effects on the EMT process and NF-κB pathway.

[RESULTS] PCDH1 was significantly overexpressed in pancreatic cancer tissues compared with normal tissues, and its expression correlated positively with pathological grade and disease progression. Knockdown of PCDH1 inhibited cell proliferation, migration, and invasion while promoting apoptosis. Conversely, overexpression of PCDH1 promoted cell proliferation, migration, and invasion. Notably, both knockdown and overexpression of PCDH1 increased apoptosis, suggesting a complex, context-dependent role in apoptotic regulation. PCDH1 suppressed E-cadherin expression and promoted N-cadherin and vimentin, driving EMT progression. Additionally, PCDH1 activated the NF-κB pathway by promoting nuclear translocation of P65, and inhibition of NF-κB with SC75741 reversed PCDH1-induced EMT, confirming that PCDH1 promotes pancreatic cancer metastasis via the NF-κB/EMT axis.

[CONCLUSION] PCDH1 acts as an oncogene in pancreatic cancer, promoting cell invasion, migration, and EMT progression through the NF-κB signaling pathway, making it a potential therapeutic target.