Benzophenone-3 promotes luminal breast cancer progression via activation of the ERα/E2F1/RPA3 axis.
TL;DR
It is reported that BP3 exposure potently stimulates both proliferative and migratory capacities of BC cells, concomitantly accelerating the acquisition of aggressive malignant traits.
Abstract
As one of the leading causes of cancer-related mortality among women globally, breast cancer (BC) has been increasingly linked to environmental risk factors. Among these, Benzophenone-3 (BP3)-a ubiquitous ultraviolet filter-has drawn research interest, yet its specific contributions to BC pathogenesis remain poorly defined. Here we report that BP3 exposure potently stimulates both proliferative and migratory capacities of BC cells, concomitantly accelerating the acquisition of aggressive malignant traits. Through transcriptomic profiling, we identified a set of differentially regulated transcripts upon BP3 treatment, with Gene Ontology analysis pointing to enhanced epithelial proliferation, induction of epithelial-mesenchymal transition, and suppressed cell-adhesion programs. A prognostic risk model derived from LASSO regression of BP3-responsive genes demonstrated significant association with patient survival outcomes. Mechanistically, we pinpoint replication protein A3 (RPA3) as an essential downstream effector, since its depletion largely abolished the pro-tumorigenic effects elicited by BP3. Further dissection of the regulatory circuit revealed that BP3 drives RPA3 upregulation through the ERα/E2F1 transcriptional axis. Collectively, these data establish BP3 as an environmental promoter of BC malignancy and implicate the ERα/E2F1/RPA3 cascade as a potential therapeutic vulnerability. Given its widespread use, these findings raise public health concerns about chronic BP3 exposure and support further evaluation of its long-term safety.