Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

Cancer Med. 2016 Aug;5(8):2061-8. doi: 10.1002/cam4.772. Epub 2016 May 26.

Abstract

Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threonine-tyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signal-regulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment.

Keywords: Carcinogenesis; DUSP1/MKP1; JNK; tumor therapy.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Combined Modality Therapy
  • Disease Progression
  • Dual Specificity Phosphatase 1 / genetics*
  • Dual Specificity Phosphatase 1 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects

Substances

  • Dual Specificity Phosphatase 1