Targeting Overexpressed Activating Transcription Factor 1 (ATF1) Inhibits Proliferation and Migration and Enhances Sensitivity to Paclitaxel In Esophageal Cancer Cells

Med Sci Monit Basic Res. 2017 Sep 15:23:304-312. doi: 10.12659/MSMBR.906289.

Abstract

Background: Previous reports showed that Activating Transcription Factor 1 (ATF1) plays an important role in tumor progression in a tumor-specific manner. However, little is known about the expression and role of ATF1 in esophageal cancer.

Material/Methods: The expression of ATF1 was examined by immunohistochemistry and Western blotting. The correlation between the expression of ATF1 and clinical characteristics of esophageal squamous cell carcinomas (ESCC) patients was analyzed by Fisher’s exact test. The role of cell proliferation, clonogenic survival, migration, and invasion in vitro, as well as the sensitization to paclitaxel, were determined after knockdown of ATF1 by siRNA.

Results: ATF1 was overexpressed in ESCC tissues, which was positively correlated with lymph node metastasis, poor differentiation, and early tumor invasion of esophageal cancer patients. Knockdown of ATF1 effectively reduced cell proliferation, induced S phase cell cycle arrest, and inhibited cell migration and invasion. Moreover, silencing of ATF1 significantly enhanced the sensitivity of esophageal cancer cells to paclitaxel.

Conclusions: These findings suggest that ATF1 is a promising drug target for esophageal cancer.

Keywords: Activating Transcription Factor 1; Cell Migration Assays; Cell Proliferation; Esophageal Neoplasms.

MeSH terms

  • Activating Transcription Factor 1 / genetics
  • Activating Transcription Factor 1 / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Humans
  • Paclitaxel / pharmacology
  • Phosphorylation

Substances

  • ATF1 protein, human
  • Activating Transcription Factor 1
  • Paclitaxel