A research of STEAP1 regulated gastric cancer cell proliferation, migration and invasion in vitro and in vivos

J Cell Mol Med. 2020 Dec;24(24):14217-14230. doi: 10.1111/jcmm.16038. Epub 2020 Oct 30.

Abstract

Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumour growth and metastasis, as well as its molecular mechanism of action.Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion;For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. In the results,we found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single-factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Up-regulation of STEAP1 increased cell proliferation, migration and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumour and peritoneal tumour formation.

Keywords: STEAP1; gastric cancer; invasion; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Prognosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Tumor Burden

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Oxidoreductases
  • STEAP1 protein, human