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

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

  • Ecotoxicol Environ Saf. 2025 Dec 15:309:119536. doi: 10.1016/j.ecoenv.2025.119536.
Shiyan Lao 1,  Jianlong Xie 2,  Yongfang Ou 3,  Haoyong Liu 4,  Qiujuan Fu 5,  Jiahuan Wu 6,  Lingling Qin 7,  Ruiyin Li 7,  Kaiqi Zeng 6,  Sihan Wang 6,  Lingdiao Zeng 8
Affiliations

Affiliations

  • 1 Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524003, China; Emergency Center, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524003, China. Electronic address: [email protected].
  • 2 Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China. Electronic address: [email protected].
  • 3 Pathology Diagnosis Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China. Electronic address: [email protected].
  • 4 Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524003, China.
  • 5 Pathology Diagnosis Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.
  • 6 First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
  • 7 Pathology Diagnosis Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China; First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
  • 8 Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524003, China. Electronic address: [email protected].
PMID: 41401551 DOI: 10.1016/j.ecoenv.2025.119536
Abstract

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.

Keywords

Breast Cancer; F-53B; HIF-1α; PKM2.

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