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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Bladder transitional cell carcinoma (BTCC) cell migration is a critical factor in cancer progression and metastasis.
• Fatty acid synthase complex (FASN) is implicated in various cancers, but its role in BTCC cell migration requires further elucidation.
• Matrix metalloproteinase-9 (MMP-9) is a key enzyme involved in extracellular matrix degradation and cancer cell invasion.

Purpose of the Study:

• To investigate the effect of FASN on BTCC cell migration.
• To determine the involvement of phospho-AKT (p-AKT) and MMP-9 in FASN-mediated BTCC cell migration.
• To evaluate FASN inhibition as a potential therapeutic strategy for BTCC.

Main Methods:

• FASN gene expression was inhibited in BTCC cell lines (5637 and 253J) using FASN-specific small-interfering RNA (FASN-siRNA).
• Cell migration was assessed using Transwell assays.
• Protein and mRNA levels of FASN, p-AKT, AKT, and MMP-9 were analyzed via Western blot and other analyses.

Main Results:

• FASN inhibition using FASN-siRNA and a chemical inhibitor (Cer) significantly decreased BTCC cell migratory capacity.
• FASN inhibition led to reduced levels of p-AKT and decreased expression of MMP-9.
• These findings suggest a pathway where FASN affects AKT activation, subsequently influencing MMP-9 expression and cell migration.

Conclusions:

• FASN inhibition suppresses the migratory capacity of BTCC cells.
• The mechanism involves the downregulation of AKT activation and consequently, reduced MMP-9 expression.
• Targeting FASN presents a promising therapeutic avenue for bladder transitional cell carcinoma.