Visfatin-induced upregulation of lipogenesis via EGFR/AKT/GSK3 β pathway promotes breast cancer cell growth

Cell Signal. 2023 Apr 19:110686. doi: 10.1016/j.cellsig.2023.110686. Online ahead of print.ABSTRACTBreast cancer (BC) incidence and associated mortality have increased in tandem with the growth in obesity among the females worldwide. An adipokine, visfatin, has been shown to potentially impact glucose, lipid, and protein metabolism, and promote cancer growth however, the mechanism underlying the effect of visfatin on lipid metabolism dysregulation contributing to BC cell survival, proliferation, and metastasis has not been elucidated. Herein, we have investigated the role of visfatin on the induction of Sterol regulatory element binding protein (SREBP-1) and its upstream and downstream mediators in MCF-7 breast cancer cells. The survival and proliferation was investigated using MTT and Trypan blue assays, cytosolic lipid accumulation was observed using Nile red staining, mRNA and protein expressions were examined using RT-qPCR and western blotting, respectively, and cell cycle analysis was performed using fluorescence-activated cell sorting. Our results indicate that visfatin increased the survival and proliferation of MCF-7 cells in a time- and dose-dependent manner and augmented lipid buildup via activation of SREBP-1 and its associated downstream lipid synthesizing enzymes, at both mRNA and protein levels in MCF-7 cells. Inhibiting SREBP-1 using fatostatin or silencing with siRNA abrogated excessive lipid deposition by suppressing the expression of genes related to lipid s...
Source: Cellular Signalling - Category: Cytology Authors: Source Type: research