Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway

Title:Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway

Volume: 21 Issue: 18

Author(s): Huiming Chen, Junfeng Zhao, Ningning Jiang, Zheng Wang* Chang Liu*

Affiliation:

• Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061,China

• Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061,China

Keywords: Pancreatic ductal adenocarcinoma, hyperglycemia, Wnt/β-catenin, signaling pathway, tumor initiation and progression, pancreatic cancer.

Abstract:

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a 5- year survival rate of less than 10% because of the limited knowledge of tumor-promoting factors and their underlying mechanism. Diabetes mellitus (DM) and hyperglycemia are risk factors for many cancers, including PDAC, that modulate multiple downstream signaling pathways, such as the wingless/integrated (Wnt)/β-- catenin signaling pathway. However, whether hyperglycemia promotes PDAC initiation and progression by activating the Wnt/β-catenin signaling pathway remains unclear.

Methods: In this study, we used bioinformatics analysis and clinical specimen analysis to evaluate the activation states of the Wnt/β-catenin signaling pathway. In addition, colony formation assays, Transwell assays and wound-healing assays were used to evaluate the malignant biological behaviors of pancreatic cancer cells (PCs) under hyperglycemic conditions. To describe the effects of hyperglycemia and the Wnt/β-catenin signaling pathway on the initiation of PDAC, we used pancreatitis-driven pancreatic cancer initiation models in vivo and pancreatic acinar cell 3-dimensional culture in vitro.

Results: Wnt/β-catenin signaling pathway-related molecules were overexpressed in PDAC tissues/cells and correlated with poor prognosis in PDAC patients. In addition, hyperglycemia exacerbated the abnormal activation of β-catenin in PDAC and enhanced the malignant biological behaviors of PCs in a Wnt/β-catenin signaling pathway-dependent manner. Indeed, hyperglycemia accelerated the formation of precancerous pancreatic lesions by activating the Wnt/β-catenin signaling pathway in vivo and in vitro.

Conclusion: Hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β- catenin signaling pathway.

Cite this article as:

Chen Huiming , Zhao Junfeng, Jiang Ningning , Wang Zheng *, Liu Chang*, Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway, Anti-Cancer Agents in Medicinal Chemistry 2021; 21 (18) . https://dx.doi.org/10.2174/1871520621666210201095613