Downregulation of fatty acid synthase complex suppresses cell migration by targeting phosphor-AKT in bladder cancer

脂肪酸合酶复合物的下调通过靶向磷酸化 AKT 来抑制膀胱癌中的细胞迁移

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作者:Shuai-Shuai Zheng, Jian-Gang Gao, Zhi-Jun Liu, Xin-Hong Zhang, Shuai Wu, Bo-Wen Weng, You-Lin Wang, Si-Chuan Hou, Bo Jiang

Abstract

The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase‑9 (MMP‑9) via targeting of phospho‑AKT (p‑AKT). FASN‑specific small‑interfering RNA (FASN‑siRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAM‑conjugated FASN‑siRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, p‑AKT, AKT, and migration‑associated protein MMP‑9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASN‑siRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of p‑AKT as well as the expression of MMP‑9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP‑9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.

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