2. Academic Validation
  3. Sciellin inhibits senescence and promotes pancreatic cancer progress by activating the notch signaling pathway

Sciellin inhibits senescence and promotes pancreatic cancer progress by activating the notch signaling pathway

  • Sci Rep. 2025 May 8;15(1):16133. doi: 10.1038/s41598-025-88265-0.
Changhao Wu # 1 2 3 4 5,  Dan Luo # 1 2 4 5 6,  Binbin Shi 2 4 5,  Shiyu Chen 7,  Chengyi Sun 1 2 3 4 5,  Zhiwei He 8 9 10 11,  Chao Yu 12 13 14 15 16
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, China.
  • 2 College of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, China.
  • 3 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, 550001, China.
  • 4 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, Guiyang, 550001, China.
  • 5 Guizhou Provincial Clinical Medical Research Center of Hepatobiliary Surgery, Guiyang, 550004, Guizhou, China.
  • 6 Department of Hepatobiliary Surgery, People's Hospital of the Guizhou Province, Guiyang, 550003, China.
  • 7 Department of Hepatic-Biliary-Pancreatic Surgery, Medical School, South China Hospital, Shenzhen University, Shenzhen, 518116, China.
  • 8 Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, China. 2268272794@qq.com.
  • 9 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, 550001, China. 2268272794@qq.com.
  • 10 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, Guiyang, 550001, China. 2268272794@qq.com.
  • 11 Guizhou Provincial Clinical Medical Research Center of Hepatobiliary Surgery, Guiyang, 550004, Guizhou, China. 2268272794@qq.com.
  • 12 Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, China. yuchao2002@gmc.edu.cn.
  • 13 College of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, China. yuchao2002@gmc.edu.cn.
  • 14 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, 550001, China. yuchao2002@gmc.edu.cn.
  • 15 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, Guiyang, 550001, China. yuchao2002@gmc.edu.cn.
  • 16 Guizhou Provincial Clinical Medical Research Center of Hepatobiliary Surgery, Guiyang, 550004, Guizhou, China. yuchao2002@gmc.edu.cn.
  • # Contributed equally.
PMID: 40341648 DOI: 10.1038/s41598-025-88265-0
Abstract

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.

Keywords

Jagged-1; Notch signaling pathway; Pancreatic cancer; SCEL; Senescence.

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