Wu Changhao, Luo Dan, Shi Binbin, Chen Shiyu, Sun Chengyi, He Zhiwei, Yu Chao
Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, China.
College of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, China.
Sci Rep. 2025 May 8;15(1):16133. doi: 10.1038/s41598-025-88265-0.
Pancreatic cancer (PC) incidence is increasing annually globally, and the five-year survival rate of patients with PC is approximately 10%. Cellular senescence is a regulatory mechanism against cancer that prevents tumor development by inhibiting the proliferation of damaged or abnormal cells. However, the mechanisms underlying cellular senescence in PC is unclear. Sciellin (SCEL) is a precursor protein of the cornified envelope predominantly enriched in epithelial cells. Previous studies have discovered potential links between SCEL and cellular senescence through bioinformatics analysis. Therefore, the specific role of SCEL in cellular senescence and the malignant features of PC are unclear. In vivo and in vitro assays were performed to investigate the role of SCEL in PC cell senescence, proliferation, invasion, and metastasis. Gene set enrichment analysis was used to identify the Notch signaling pathways activated by SCEL, and coimmunoprecipitation was used to detect proteins that interact with SCEL. The results revealed that SCEL was significantly upregulated in PC tissues and cell models and was correlated with poor clinical outcomes. Further investigation revealed that the interaction between SCEL and Jagged-1 promotes the activation of the Notch signaling pathway, effectively inhibiting the senescence of PC cells while enhancing their proliferation, invasion, and metastatic capabilities. Therefore, SCEL is a potential therapeutic target for PC.
全球范围内，胰腺癌（PC）的发病率逐年上升，PC患者的五年生存率约为10%。细胞衰老作为一种抗癌调节机制，通过抑制受损或异常细胞的增殖来阻止肿瘤发展。然而，PC中细胞衰老的潜在机制尚不清楚。丝聚蛋白（SCEL）是一种主要在上皮细胞中富集的角质包膜前体蛋白。先前的研究通过生物信息学分析发现了SCEL与细胞衰老之间的潜在联系。因此，SCEL在细胞衰老和PC恶性特征中的具体作用尚不清楚。进行体内和体外实验以研究SCEL在PC细胞衰老、增殖、侵袭和转移中的作用。基因集富集分析用于鉴定由SCEL激活的Notch信号通路，免疫共沉淀用于检测与SCEL相互作用的蛋白质。结果显示，SCEL在PC组织和细胞模型中显著上调，且与不良临床预后相关。进一步研究表明，SCEL与Jagged-1之间的相互作用促进了Notch信号通路的激活，有效抑制了PC细胞的衰老，同时增强了其增殖、侵袭和转移能力。因此，SCEL是PC的一个潜在治疗靶点。
