Suppression of pancreatic cancer proliferation through TXNIP-mediated inhibition of the MAPK signaling pathway

Acta Biochim Biophys Sin (Shanghai). 2024 Apr 25;56(4):513-524. doi: 10.3724/abbs.2023286.

Abstract

Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.

Keywords: MAPK signaling pathway; TXNIP; pancreatic cancer.

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Liver Neoplasms* / pathology
  • Pancreatic Neoplasms* / metabolism
  • Signal Transduction
  • Thioredoxins / genetics
  • Thioredoxins / metabolism

Substances

  • Thioredoxins
  • TXNIP protein, human
  • Carrier Proteins

Grants and funding

This work was jointly supported by the grants the National Natural Science Foundation of China (Nos. U21A20374 and 82173091), the Shanghai Municipal Science and Technology Major Project (No. 21JC1401500), the Scientific Innovation Project of the Shanghai Education Committee (No. 2019-01-07-00-07-E00057), the Clinical Research Plan of the Shanghai Hospital Development Center (No. SHDC2020CR1006A), the Xuhui District Artificial Intelligence Medical Hospital Cooperation Project (No. 2021-011), the Shanghai Natural Science Foundation (No. 22ZR1412900), the Research Project of Shanghai Municipal Health Commission (No. 20214Y0396), and the Shanghai Pujiang Program (No. 2021PJD014).