Recent advances in PTP1B signaling in metabolism and cancer

Biosci Rep. 2021 Nov 26;41(11):BSR20211994. doi: 10.1042/BSR20211994.

Abstract

Protein tyrosine phosphorylation is one of the major post-translational modifications in eukaryotic cells and represents a critical regulatory mechanism of a wide variety of signaling pathways. Aberrant protein tyrosine phosphorylation has been linked to various diseases, including metabolic disorders and cancer. Few years ago, protein tyrosine phosphatases (PTPs) were considered as tumor suppressors, able to block the signals emanating from receptor tyrosine kinases. However, recent evidence demonstrates that misregulation of PTPs activity plays a critical role in cancer development and progression. Here, we will focus on PTP1B, an enzyme that has been linked to the development of type 2 diabetes and obesity through the regulation of insulin and leptin signaling, and with a promoting role in the development of different types of cancer through the activation of several pro-survival signaling pathways. In this review, we discuss the molecular aspects that support the crucial role of PTP1B in different cellular processes underlying diabetes, obesity and cancer progression, and its visualization as a promising therapeutic target.

Keywords: Cancer; Protein Tyrosine Phosphatase 1B; Receptor Tyrosine Kinase; Signaling; Small molecule inhibitor.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / etiology*
  • Metabolic Diseases / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / chemistry
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
  • Signal Transduction* / drug effects

Substances

  • Enzyme Inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1