Perfluorooctane sulfonate (PFOS) triggers migration and invasion of esophageal squamous cell carcinoma cells via regulation of Zeb1

Drug Chem Toxicol. 2022 Nov;45(6):2804-2813. doi: 10.1080/01480545.2021.1991775. Epub 2021 Nov 3.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly cancers worldwide, especially in Eastern Asia. As a potential endocrine-disrupting chemical (EDC), perfluorooctane sulfonate (PFOS) can mimic estrogen, disturb the estrogen signals, and then cause various diseases. Although ESCC can be directly exposed to PFOS during food digestion, the effects and mechanisms of PFOS on the development of ESCC are still not well illustrated. This study showed that PFOS can promote the migration and invasion of ESCC cells. Further, PFOS treatment can increase the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while decreasing the expression of E-Cadherin (E-Cad). Zeb1, an important transcription factor for cell motility, was essential for PFOS induced migration and invasion of ESCC cells. PFOS can increase the expression of Zeb1 via upregulation of its transcription and proteins stability. A-kinase interacting protein 1 (AKIP1) and ataxia-telangiectasia mutated (ATM) were responsible for PFOS induced transcription and proteins stability of Zeb1 in ESCC cells, respectively. Collectively, our data indicated that environmental exposure and body accumulation of PFOS might be an important risk factor for ESCC progression.

Keywords: AKIP1; ATM; ESCC; PFOS; Zeb1.

MeSH terms

  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Esophageal Neoplasms* / chemically induced
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / chemically induced
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Estrogens
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Matrix Metalloproteinase 2
  • perfluorooctane sulfonic acid
  • Matrix Metalloproteinase 9
  • Zinc Finger E-box-Binding Homeobox 1
  • Cadherins
  • Transcription Factors
  • Estrogens
  • ZEB1 protein, human
  • AKIP1 protein, human