Abstract
Perfluorooctanoic acid (PFOA) is a common environmental pollutant that has been associated with various diseases, including cancer. We explored the molecular mechanisms underlying PFOA-induced endometrial cancer cell invasion and migration. PFOA treatment enhanced migration and invasion by human Ishikawa endometrial cancer cells, which correlated with decreased E-cadherin expression, a marker of epithelial-mesenchymal transition. PFOA also induced activation of ERK1/2/mTOR signaling. Treatment with rapamycin, an mTOR inhibitor, antagonized the effects of PFOA and reversed the effects of PFOA activation in a xenograft mouse model of endometrial cancer. Consistent with these results, pre-treatment with rapamycin abolished PFOA-induced down-regulation of E-cadherin expression. These results indicate that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling.
Highlights
Perfluorooctanoic acid (PFOA) is a synthetic and persistent organic pollutant found in the environment
PFOA significantly stimulated invasion of the Ishikawa cells through the membranes of the Transwell chambers, which was further confirmed by measuring the optical density (OD) of the invaded cells. These results indicated that PFOA treatment promoted both the migration and invasion of endometrial cancer cells
We demonstrated that PFOA could enhance human Ishikawa endometrial cancer cell migration and invasion in vitro (Figure 1 and 4) and tumorigenesis in vivo (Figure 6)
Summary
Perfluorooctanoic acid (PFOA) is a synthetic and persistent organic pollutant found in the environment. Because it is stain- and water-resistant, it is widely used in manufacturing and is found in nearly everything in the environment including drinking water [1, 2]. The side effects of PFOA contamination have attracted increasing attention [3, 4]. PFOA has been associated with multiple diseases including cardiovascular disease, peripheral arterial disease, liver damage, birth defects, and cancer [2, 5,6,7]. The relationship between PFOA exposure and endometrial cancer has not been elucidated
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