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

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.
AuthorsYaqing Liu, Jian Li, Hui Ding, Dahe Ge, Juntao Wang, Chunjin Xu
JournalDrug and chemical toxicology (Drug Chem Toxicol) Vol. 45 Issue 6 Pg. 2804-2813 (Nov 2022) ISSN: 1525-6014 [Electronic] United States
PMID34732098 (Publication Type: Journal Article)
Chemical References
  • 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
Topics
  • Humans
  • Esophageal Squamous Cell Carcinoma (chemically induced, genetics, pathology)
  • Matrix Metalloproteinase 2 (metabolism)
  • Matrix Metalloproteinase 9 (metabolism)
  • Esophageal Neoplasms (chemically induced, genetics, pathology)
  • Zinc Finger E-box-Binding Homeobox 1 (genetics, metabolism)
  • Neoplasm Invasiveness (genetics)
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor
  • Cadherins (metabolism)
  • Transcription Factors (genetics, metabolism)
  • Estrogens
  • Cell Proliferation

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