Zhang Liuxi, Wei Fang, Sun Qihui, Huang Xinyan, Zou Qi, Jiang Mengmeng, Su Yuling, Li Shu, Li Xiaojia, Xie Keping, He Jie
Guangzhou First People's Hospital and The Second Affiliated Hospital, South China University of Technology School of Medicine, #1 Panfu Road, Guangzhou, Guangdong 510180, P.R. China.
Center for Pancreatic Cancer Research, South China University of Technology College of Medicine, 382 Waihuan Road, Guangzhou, Guangdong 510006, P.R. China.
Int J Biol Sci. 2025 Jan 13;21(3):1047-1064. doi: 10.7150/ijbs.105289. eCollection 2025.
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.
胰腺导管腺癌（PDAC）仍然是一种高度致命的恶性肿瘤，治疗选择有限。研究新的治疗靶点并了解化疗耐药机制对于改善患者预后至关重要。本研究调查了CKS1B在PDAC致癌、干性和化疗耐药中的作用，并探讨了其上调的潜在机制。这些发现可能为PDAC的治疗提供新的治疗见解和潜在策略。在PDAC组织和细胞系中分析了CKS1B的表达，通过使用[具体实验名称1]和[具体实验名称2]模型评估其对细胞增殖、迁移、凋亡、干性和化疗敏感性的影响，并使用分子生物学方法探索其与转录因子FOXM1的潜在机制联系。CKS1B在PDAC组织中显著上调，且与患者预后不良相关。CKS1B促进PDAC细胞增殖、迁移并抑制凋亡。CKS1B的表达增强了胰腺癌的干性特性。敲低CKS1B使PDAC细胞对吉西他滨和奥沙利铂治疗敏感。机制上，CKS1B受FOXM1转录调控，建立了一个新的FOXM1-CKS1B信号轴，该信号轴调节PDAC的致癌、增殖、迁移、干性、凋亡和耐药性。我们的研究结果强烈表明，CKS1B在PDAC进展、干性和化疗耐药中起关键作用。靶向FOXM1-CKS1B轴代表了一种有前景的PDAC患者治疗策略。
