Bisphenol A Exacerbates Colorectal Cancer Progression through Enhancing Ceramide Synthesis

Xu Hong; Sheng Wang; Qing Zhang; Lanlan Li; Hang Liu; Hongxu Yang; Danyang Wu; Xingcun Liu; Tong Shen

doi:10.1016/j.tox.2025.154054

Bisphenol A Exacerbates Colorectal Cancer Progression through Enhancing Ceramide Synthesis

Toxicology. 2025 Jan 12:154054. doi: 10.1016/j.tox.2025.154054. Online ahead of print.

Authors

Xu Hong¹, Sheng Wang², Qing Zhang¹, Lanlan Li¹, Hang Liu¹, Hongxu Yang¹, Danyang Wu¹, Xingcun Liu³, Tong Shen⁴

Affiliations

¹ Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China.
² Center for Scientific Research of Anhui Medical University, Hefei 230032, Anhui, PR China.
³ Department of Gastrointestinal surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui, PR China.
⁴ Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China. Electronic address: shentong@ahmu.edu.cn.

PMID: 39809339
DOI: 10.1016/j.tox.2025.154054

Abstract

Bisphenol A (BPA) is a typical environmental endocrine disruptor which have been broadly confirmed to be associated with malignant tumors, including colorectal cancer (CRC). Lipid metabolism reprogramming performed important biological effects in cancer progression. While the role of lipid metabolism in CRC progression upon BPA exposure remain elusive. Here, we found that BPA exposure enhanced de novo ceramide synthesis in vitro, along with upregulated ceramide synthase in high-BPA tumor tissue of CRC patients. Simultaneously, we demonstrated that BPA exposure exacerbated tumor biological behavior and epithelial mesenchymal transition (EMT), concurrent with elevated EMT expression of CRC tissue in high BPA group. Subsequently, the inhibition of ceramide synthase and pharmacological stimulation experiments revealed that ceramide accumulation activated EMT and exacerbated CRC progression, including Cer (d18:1/16:0) and Cer (d18:1/24:1). Collectively our findings elucidated the pathogenesis of ceramide accumulation escalating tumor progression under environmental BPA exposure, providing a strong basis for further investigation of dysregulated ceramide metabolism to boost tumor development and avoid metastatic relapse.

Keywords: BPA; ceramide metabolism; colorectal cancer.