Fatty Acid Binding Protein 6 Inhibition Decreases Cell Cycle Progression, Migration and Autophagy in Bladder Cancers

Abstract

Bladder cancer (BC) has a high recurrence rate worldwide. The aim of this study was to evaluate the role of fatty acid binding protein 6 (FABP6) in proliferation and migration in human bladder cancer cells. Cell growth was confirmed by MTT and colony formation assay. Western blotting was used to explore protein expressions. Wound healing and Transwell assays were performed to evaluate the migration ability. A xenograft animal model with subcutaneous implantation of BC cells was generated to confirm the tumor progression. Knockdown of FABP6 reduced cell growth in low-grade TSGH-8301 and high-grade T24 cells. Cell cycle blockade was observed with the decrease of CDK2, CDK4, and Ki67 levels in FABP6-knockdown BC cells. Interestingly, knockdown of FBAP6 led to downregulation of autophagic markers and activation of AKT-mTOR signaling. The application of PI3K/AKT inhibitor decreased cell viability mediated by FABP6-knockdown additionally. Moreover, FABP6-knockdown reduced peroxisome proliferator-activated receptor γ and retinoid X receptor α levels but increased p-p65 expression. Knockdown of FABP6 also inhibited BC cell motility with focal adhesive complex reduction. Finally, shFABP6 combined with cisplatin suppressed tumor growth in vivo. These results provide evidence that FABP6 may be a potential target in BC cells progression.

A bile acid-related prognostic signature in hepatocellular carcinoma

“…FABP6 is a BA transporter in ileal epithelial cells and is critical for the enterohepatic circulation of BAs 25 . FABP6 also participates in the progression of numerous types of cancer [26][27][28] . Compared with adjacent normal liver tissues, overexpressed FABP6 was observed in HCC tissues 29 .…”

Autophagy in Cell Survival and Death

“…Lin et al showed that fatty acid binding protein 6 (FABP6) regulates cell cycle progression and autophagy in bladder cancer (BC) cells [3]. Knockdown of FABP6 inhibited BC cell growth via regulation of cell-cycle-related protein expressions.…”

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

“…PDGFRA and PDGFRB exert a central function in the initiation and progression of many tumors, including glioblastoma, gastrointestinal stromal tumor, skin squamous cell carcinoma, and oral squamous cell carcinoma [ 40 , 41 , 42 , 43 ]. FABP6 has been reported as a potential target for inhibiting the progression of BLCA, and the mechanism may involve several aspects, such as affecting the activation of the AKT-mTOR signal and cell cycle [ 44 ]. NRP2 exerts a key role in lymphangiogenesis and lymphovascular invasion and affects the function of epithelial–mesenchymal transformation in the evolution of tumor transmission and metastasis [ 45 , 46 ].…”