Internal Medicine Department, The First People's Hospital of Shangqiu, Shangqiu, P. R. China.
Department of Gastroenterology, Shangqiu Clinical College, Xuzhou Medical University, Shangqiu, P. R. China.
Drug Chem Toxicol. 2022 Nov;45(6):2804-2813. doi: 10.1080/01480545.2021.1991775. Epub 2021 Nov 3.
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.
食管鳞状细胞癌（ESCC）是全球最常见和最致命的癌症之一，尤其在东亚地区更为常见。全氟辛烷磺酸（PFOS）作为一种潜在的内分泌干扰化学物质，能够模拟雌激素，干扰雌激素信号，从而导致多种疾病。尽管 ESCC 可以在食物消化过程中直接接触 PFOS，但 PFOS 对 ESCC 发展的影响和机制仍未得到充分阐明。本研究表明，PFOS 可促进 ESCC 细胞的迁移和侵袭。此外，PFOS 处理可以增加基质金属蛋白酶-2（MMP-2）和 MMP-9 的表达，同时降低 E-钙黏蛋白（E-Cad）的表达。Zeb1 是细胞迁移的重要转录因子，对于 PFOS 诱导的 ESCC 细胞迁移和侵袭是必需的。PFOS 通过上调其转录和蛋白稳定性来增加 Zeb1 的表达。A-激酶相互作用蛋白 1（AKIP1）和共济失调毛细血管扩张突变（ATM）分别负责 PFOS 诱导的 Zeb1 转录和蛋白稳定性在 ESCC 细胞中的作用。综上所述，我们的数据表明，环境暴露和体内 PFOS 积累可能是 ESCC 进展的一个重要危险因素。
