Triphenyl Phosphate Exposure Is Associated With BRG1-Related Cellular and Metabolic Readouts and EREG-EGFR/ERK Signalling in Glioma Cells.

BACKGROUND

Triphenyl phosphate (TPP), a ubiquitous organophosphate flame retardant and plasticiser, has emerged as a pervasive environmental contaminant with suspected endocrine-disrupting properties.

METHODS

In this study, we employed an integrated approach combining epigenetic CRISPR-Cas9 knockout screening, spatial transcriptomics, and metabolic flux analysis to explore the response of glioma cells to in vitro exposure to a nominal TPP concentration of 11 μM. Targeted cellular, biochemical, promoter-occupancy and signalling assays were performed.

RESULTS

TPP exposure was associated with changes in several cellular readouts in glioma cells, including a higher CCK-8 signal, differences in MMP secretion, Rac1 activity and matrix adhesion and differences in glucose, lactate and mitochondrial-respiration readouts. TPP exposure was also associated with increased BRG1 occupancy at the assayed epidermal growth factor receptor (EGFR) promoter region, together with higher EGFR- and epiregulin (EREG)-related readouts. This pattern is consistent with a candidate EREG-EGFR/MAPK-ERK pathway association but does not prove a self-sustaining loop or direct chemical recruitment. Spatial transcriptomic analysis described regional heterogeneity in mitochondrial-gene expression within public glioblastoma tissue.

CONCLUSION

Our findings support a candidate BRG1-associated cellular framework in which nominal TPP exposure is associated with BRG1-related chromatin and EGFR/metabolic readouts in glioma cells.