The environmental pollutant F-53B accelerates triple-negative breast cancer progression through metabolic reprogramming.

Following the ban on perfluorooctane sulfonate (PFOS), the use of chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESA, known commercially as F-53B) has surged significantly in China. Numerous studies indicate that F-53B is increasingly detected in diverse environmental media, animals, and humans, with both its concentration and detection frequency rising annually. Humans can be exposed to F-53B through respiration, skin contact, drinking water, and dietary intake. Triple-negative breast cancer (TNBC), a highly malignant subtype with a poor prognosis, is experiencing a rising incidence rate, with environmental pollutants significantly linked to its onset and progression. This study utilized TNBC cells as a model to assess the impact of F-53B on breast cancer. Our experimental results demonstrated that F-53B could promote the proliferation of TNBC, as verified by CCK8 assay and the detection of marker molecules for cell proliferation. Further studies revealed that F-53B could increase ATP production and glucose uptake in TNBC cells. Our findings also indicated that F-53B could enhance glycolysis, as evidenced by the expression levels of PKM2, GLUT1, HK2, and LDHA. Our investigation into the molecular mechanism of F-53B in breast cancer revealed that F-53B stabilizes HIF-1α protein levels. We found that F-53B inhibits the HIF-α and VHL interaction, preventing HIF-1α degradation. Consequently, the expression of glycolysis-related enzymes increased. In conclusion, the present study identified a close association between F-53B and the onset and progression of TNBC, providing important evidence for investigating the toxicological mechanism of F-53B.