Integrin α7 high expression correlates with deteriorative tumor features and worse overall survival, and its knockdown inhibits cell proliferation and invasion but increases apoptosis in breast cancer

J Clin Lab Anal. 2019 Oct;33(8):e22979. doi: 10.1002/jcla.22979. Epub 2019 Jul 19.

Abstract

Background: This study aimed to investigate the correlation of integrin α7 (ITGA7) expression with clinical/pathological characteristics and overall survival (OS), and its knockdown on inhibiting cell activities in breast cancer.

Methods: A total of 191 breast cancer patients underwent surgery were retrospectively reviewed, and ITGA7 expression in tumor tissues was determined by immunofluorescence and real-time quantitative polymerase chain reaction. Patients' clinical/pathological data were recorded, and OS was calculated. In vitro, control shRNA and ITGA7 shRNA plasmids were transfected into MCF7 cells to evaluate the influence of ITGA7 knockdown on cell proliferation, apoptosis, and invasion.

Results: Ninety-two (48.2%) patients presented with ITGA7 high expression, and 99 patients (51.8%) presented with ITGA7 low expression. ITGA7 expression was positively correlated with T stage, tumor-node metastasis (TNM) stage, and pathological grade. Kaplan-Meier curves showed that ITGA7 high expression was associated with shorter OS, and multivariate Cox's proportional hazards regression displayed that ITGA7 high expression was an independent predictive factor for poor OS. Moreover, in vitro experiments disclosed that cell proliferation (by Cell Counting Kit-8 assay) and cell invasion (by Matrigel invasion assay) were reduced, while cell apoptosis rate (by Annexin V/propidium iodide assay) was enhanced by ITGA7 knockdown in MCF-7 cells.

Conclusion: Integrin α7 high expression correlates with increased T stage, TNM stage, and pathological grade as well as worse OS, and its knockdown enhances cell apoptosis but inhibits cell proliferation and invasion in breast cancer.

Keywords: apoptosis; breast cancer; integrin α7; proliferation; survival.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Integrin alpha Chains / antagonists & inhibitors
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Small Interfering / genetics
  • Retrospective Studies
  • Survival Rate

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • Integrin alpha Chains
  • RNA, Small Interfering
  • integrin alpha7