Polychlorinated biphenyl quinone exposure promotes breast cancer aerobic glycolysis: An in vitro and in vivo examination

Polychlorinated biphenyls (PCBs) were classified as group I carcinogenic to humans, as their toxicological mechanisms have been associated with Cancer initiation and promotion. However, whether PCBs have effects on Cancer progression are still largely veiled. Here, we for the first time discovered that a PCB quinone-type metabolite, namely PCB29-pQ, exposure significantly promoted aerobic glycolysis, a hallmark property of metabolic reprogramming in Cancer progression. PCB29-pQ exposure activated corresponding glucose transporter type 1 (GLUT1)/Integrin β1/Src/focal adhesion kinase (FAK) signaling pathway in breast Cancer MDA-MB-231 cells. Conversely, the inhibition of GLUT1 reversed this effect, as well as the ability of migration and invasion of MDA-MB-231 cells. In addition, PCB29-pQ-induced breast Cancer metastasis in 4T1-luc cell inoculated nude mice is repressed by GLUT1 inhibition. Overall, our results demonstrated a novel mechanism that PCB29-pQ exposure promotes aerobic glycolysis in both in vitro and in vivo breast Cancer models in a GLUT1-dependent fashion, which may provide a strategy to prevent breast Cancer cell spread.

Aerobic glycolysis; Breast cancer; GLUT1; Metastasis; PCBs.