| Title: | Sorcin can trigger pancreatic cancer-associated new-onset diabetes through the secretion of inflammatory cytokines such as serpin E1 and CCL5 |
| Journal: | Experimental & Molecular Medicine |
| Published: | 8 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39516378/ |
| DOI: | https://doi.org/10.1038/s12276-024-01346-4 |
Publication 14165
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
A rise in blood glucose is an early warning sign of underlying pancreatic cancer (PC) and may be an indicator of genetic events in PC progression. However, there is still a lack of mechanistic research on pancreatic cancer-associated new-onset diabetes (PCAND). In the present study, we identified a gene SRI, which possesses a SNP with the potential to distinguish PCAND and Type 2 diabetes mellitus (T2DM), by machine learning on the basis of the UK Biobank database. In vitro and in vivo, sorcin overexpression induced pancreatic β-cell dysfunction. Sorcin can form a positive feedback loop with STAT3 to increase the transcription of serpin E1 and CCL5, which may directly induce β-cell dysfunction. In 88 biopsies, the expression of sorcin was elevated in PC tissues, especially in PCAND samples. Furthermore, plasma serpin E1 levels are higher in peripheral blood samples from PCAND patients than in those from T2DM patients. In conclusion, sorcin may be the key driver in PCAND, and further study on the sorcin-STAT3-serpin E1/CCL5 signaling axis may help us better understand the pathogenesis of PCAND and identify potential biomarkers.</p>
13 Keywords
- Animals
- Calcium-Binding Proteins
- Chemokine CCL5
- Cytokines
- Diabetes Mellitus, Type 2
- Female
- Humans
- Male
- Mice
- Pancreatic Neoplasms
- Polymorphism, Single Nucleotide
- STAT3 Transcription Factor
- Serpins
18 Authors
- Jiali Gong
- Xiawei Li
- Zengyu Feng
- Jianyao Lou
- Kaiyue Pu
- Yongji Sun
- Sien Hu
- Yizhao Zhou
- Tianyu Song
- Meihua Shangguan
- Kai Zhang
- Wenjie Lu
- Xin Dong
- Jian Wu
- Hong Zhu
- Qiaojun He
- Hongxia Xu
- Yulian Wu
1 Application
| Application ID | Title |
|---|---|
| 91799 | Combining genetic, environmental and clinical information to predict the risk of gastrointestinal cancer |
Enabling scientific discoveries that improve human health