Demonstrating the effect of SHP2 inhibitor on cervical squamous cell carcinoma from the perspective of ZAP70

Anticancer Drugs. 2021 Jun 1;32(5):477-483. doi: 10.1097/CAD.0000000000001055.

Abstract

SHP2, encoded by the PTPN11 gene, plays an important role in regulating immune cell functions in tumor microenvironment. Several SHP2 inhibitors have entered the clinical trial stage, but cervical squamous cell carcinoma (CSCC) has not been included in the indications. In Tlymphocytes, SHP2 can promote the dephosphorylation of ZAP70 kinase in the T cell receptor signaling complex after recruitment to the PD-1 cytoplasmic tail. In this study, we used bioinformatics tools to confirm that ZAP70 has a widespread impact on the immunity of CSCC, which is closely related to the survival of CSCC. The effect of ZAP70 on the survival of cervical cancer may not depend on the structure or amplification, but on the enhancement of function. And we identified ZAP70 and PTPN11 protein-protein interactions. SHP2 inhibitor is worth to be studied in the treatment of CSCC.

MeSH terms

  • Carcinoma, Squamous Cell / immunology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Databases, Genetic
  • Female
  • Humans
  • Programmed Cell Death 1 Receptor / immunology
  • Protein Interaction Maps
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction
  • T-Lymphocytes / immunology
  • Uterine Cervical Neoplasms / immunology*
  • ZAP-70 Protein-Tyrosine Kinase / immunology*

Substances

  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell
  • ZAP-70 Protein-Tyrosine Kinase
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11