Pin1: Advances in pancreatic cancer therapeutic potential and inhibitors research

Bioorg Chem. 2024 Dec:153:107869. doi: 10.1016/j.bioorg.2024.107869. Epub 2024 Oct 11.

Abstract

The peptidyl-prolyl cis/trans isomerase NIMA-interaction 1 (Pin1) catalyzes the transition of the proline ring from the cis to trans conformation, resulting in conformational and functional changes in proteins that are regulated by proline-guided serine/threonine phosphorylation. In recent years, Pin1 has emerged as a novel molecular target for the diagnosis and treatment of various malignant tumors. Notably, it has been found that Pin1 is highly expressed in pancreatic cancer. This article focuses on the mechanisms by which Pin1 orchestrates multiple oncogenic functions in the development of pancreatic cancer. By exploring the intricate interactions between Pin1 and the pancreatic tumor microenvironment, we provide an overview of Pin1's role in modifying glycolytic metabolism, redox balance, and the hypoxic microenvironment of pancreatic cancer. Furthermore, we summarize the potential anticancer effects of Pin1 inhibitors, aiming to elucidate Pin1's promise as a potential anticancer agent, particularly in the context of pancreatic cancer.

Keywords: Hypoxic microenvironment; Pancreatic cancer; Peptidyl-prolyl cis/trans isomerase NIMA-interaction 1; Pin1 inhibitors; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / therapeutic use
  • Humans
  • Molecular Structure
  • NIMA-Interacting Peptidylprolyl Isomerase* / antagonists & inhibitors
  • NIMA-Interacting Peptidylprolyl Isomerase* / metabolism
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Antineoplastic Agents
  • PIN1 protein, human
  • Enzyme Inhibitors