PFKFB3 potentially contributes to paclitaxel resistance in breast cancer cells through TLR4 activation by stimulating lactate production.

In this study, we sought to examine the role of 6-Phosphofructo-2-kinase (PFKFB3), a critical regulator of glycolysis, in paclitaxel resistance development. Two clones of paclitaxel resistant breast cancer cells, MCF-7RA and MCF-7RB, were established by a long term exposure of MCF-7 cells to paclitaxel. Consequently, PFKFB3 expression was found to be increased in MCF-7RA and MCF-7RB cells compared with MCF-7 cells. Silencing PFKFB3 expression markedly reduced the IC50 concentrations of MCF-7RA and MCF-7RB cells. Moreover, PFKFB3 modulated toll like receptor 4 (TLR4) and MyD88 expression as well as interleukin (IL)-6 and IL-8 release from breast cancer cells in response to paclitaxel exposure. In addition, PFKFB3 overexpression boosted up fructose-2,6-bisphosphate (F2,6BP) and lactate production. The enhanced lactate contributed to TLR4 signaling activation, IL-6 and IL-8 generation, and cell viability promotion in MCF-7 cells. In all, we characterized the novel role of PFKFB3 in induction of paclitaxel resistance by raising lactate production and activating TLR4 signaling. PMID: 27262815 [PubMed - as supplied by publisher]
Source: Cellular and Molecular Biology - Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research