Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells

Cancer Lett. 2020 Feb 1:470:106-114. doi: 10.1016/j.canlet.2019.10.043. Epub 2019 Oct 31.

Abstract

Pin1 is one member of a group consisting of three prolyl isomerases. Pin1 interacts with the motif containing phospho-Ser/Thr-Pro of substrates and enhances cis-trans isomerization of peptide bonds, thereby controlling the functions of these substrates. Importantly, the Pin1 expression level is highly upregulated in most cancer cells and correlates with malignant properties, and thereby with poor outcomes. In addition, Pin1 was revealed to promote the functions of multiple oncogenes and to abrogate tumor suppressors. Accordingly, Pin1 is well recognized as a master regulator of malignant processes. Recent studies have shown that Pin1 also binds to a variety of metabolic regulators, such as AMP-activated protein kinase, acetyl CoA carboxylase and pyruvate kinase2, indicating Pin1 to have major impacts on lipid and glucose metabolism in cancer cells. In this review, we focus on the roles of Pin1 in metabolic reprogramming, such as "Warburg effects", of cancer cells. Our aim is to introduce these important roles of Pin1, as well as to present evidence supporting the possibility of Pin1 inhibition as a novel anti-cancer strategy.

Keywords: AMP-Activated kinase (AMPK); Acetyl CoA carboxylase; HIF1; Pin1; Pyruvate kinase M2; Warburg effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Proliferation
  • Glucose / metabolism
  • Glycolysis*
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • Mice
  • Mice, Knockout
  • NIMA-Interacting Peptidylprolyl Isomerase / antagonists & inhibitors
  • NIMA-Interacting Peptidylprolyl Isomerase / genetics
  • NIMA-Interacting Peptidylprolyl Isomerase / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Proto-Oncogene Proteins c-myc / metabolism

Substances

  • Antineoplastic Agents
  • Hypoxia-Inducible Factor 1
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Proto-Oncogene Proteins c-myc
  • PIN1 protein, human
  • Pin1 protein, mouse
  • Glucose