Targeting Fibrosis: The Bridge That Connects Pancreatitis and Pancreatic Cancer

Abstract

Pancreatic fibrosis is caused by the excessive deposits of extracellular matrix (ECM) and collagen fibers during repeated necrosis to repair damaged pancreatic tissue. Pancreatic fibrosis is frequently present in chronic pancreatitis (CP) and pancreatic cancer (PC). Clinically, pancreatic fibrosis is a pathological feature of pancreatitis and pancreatic cancer. However, many new studies have found that pancreatic fibrosis is involved in the transformation from pancreatitis to pancreatic cancer. Thus, the role of fibrosis in the crosstalk between pancreatitis and pancreatic cancer is critical and still elusive; therefore, it deserves more attention. Here, we review the development of pancreatic fibrosis in inflammation and cancer, and we discuss the therapeutic strategies for alleviating pancreatic fibrosis. We further propose that cellular stress response might be a key driver that links fibrosis to cancer initiation and progression. Therefore, targeting stress proteins, such as nuclear protein 1 (NUPR1), could be an interesting strategy for pancreatic fibrosis and PC treatment.

Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic β-cell failure

“…Instead, the pancreatic tissue of aged NRK1 KO mice was characterized by lower islet counts, reduced islet size and exacerbated fibrosis, ultimately leading to a failure in secreting sufficient insulin upon glucose challenges. The development of age-related pancreatic fibrosis is well documented in the literature [ 54 ] and is largely triggered by reactive oxygen species (ROS)- and inflammation-driven activation of pancreatic stellate cells [ 55 ]. Interestingly, fibrotic tissues display reduced NAD + content, and the supplementation with NAD + precursors has been shown to prevent the development of fibrosis in kidney and liver, irrespectively of whether it was induced by diet, pharmacological agents or genetic manipulations [ [56] , [57] , [58] , [59] ].…”

The interplay of transcriptional coregulator NUPR1 with SREBP1 promotes hepatocellular carcinoma progression via upregulation of lipogenesis

“…Another limitation in this study was that NUPR1 was expressed mainly in the areas surrounding the inflammatory infiltrates or fibroblast infiltration based on our IHC staining results. In addition, NUPR1 has been reported to play a crucial role in the fibrosis of the liver, pancreas and kidney [ 15 , 29 , 30 ]. There may be a close relationship between NUPR1 and the microenvironment in chronic hepatitis and liver cancer progression.…”

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression

“…Fibrosis is believed to be a critically important driver in promoting the transition of chronic pancreatitis into pancreatic cancer. NUPR1 may be a critical transcription factor which is induced in response to the cellular stress and could be a therapeutic target in pancreatic cancer progression [ 161 ].…”