FOXM1-Driven CKS1B Upregulation Promotes Pancreatic Cancer Progression and Therapeutic Resistance.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited treatment options. Investigating novel therapeutic targets and understanding mechanisms of chemoresistance are crucial for improving patient outcomes. This study investigated the role of CKS1B in PDAC carcinogenesis, stemness and chemoresistance, and explores the underlying mechanisms driving its upregulation. The findings may provide novel therapeutic insights and potential strategies for the treatment of PDAC. CKS1B expression was analyzed in PDAC tissues and cell lines, its impact on cell proliferation, migration, apoptosis, stemness and chemosensitivity were evaluated by using and models, and its underlying mechanistic connection to transcription factor FOXM1 was explored by using molecular biology methods. CKS1B was significantly upregulated in PDAC tissues and correlated with poor patient survival. CKS1B promoted PDAC cell proliferation, migration, and inhibited apoptosis. Expression of CKS1B enhanced the stemness properties of pancreatic cancer. CKS1B knockdown sensitized PDAC cells to the treatment of gemcitabine and oxaliplatin. Mechanistically, CKS1B is transcriptionally regulated by FOXM1, establishing a novel FOXM1-CKS1B signaling axis that regulates carcinogenesis, proliferation, migration, stemness, apoptosis, and drug resistance in PDAC. Our findings strongly suggest that CKS1B plays a critical role in PDAC progression, stemness and chemoresistance. Targeting the FOXM1-CKS1B axis represents a promising therapeutic strategy for PDAC patients.