FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis.
<b>Conclusion:</b> FASN enhanced CRC cell proliferation and metastasis potentially through AMPK/mTOR pathway, indicating that FASN/AMPK/mTOR signaling axis may serve as a potential target for the treatment of CRC.
However, the contribution of FASN-mediated upregulation of sphingolipid metabolism to colorectal cancer metastasis and the potential of these pathways as targets for therapeutic intervention remain unknown.
The biological experimental results indicated that 8u also blocked PI3K/Akt pathway, thereby reducing fatty acid synthase (FASN) protein expression and disordering intracellular lipid metabolism to inhibit cell invasion and metastasis.
Coexpression of fatty acid binding protein (FABP1) and fatty acid synthase (FASN) in gastric cancer tissues (61.4% sensitivity and 77.1% specificity) was strongly associated with lymph node metastasis and Tumor, Node, Metastasis stage I/II.
Results demonstrated that the knockdown of FASN markedly suppressed the growth and metastasis of OS, at least partially, by blocking the HER2/PI3K/Akt signal pathway in mice with intratibial 143B OS xenografts.
Taken together, it was suggested that FASN was closely associated with GC metastasis and survival, which further provided evidence that FASN may be a promising prognostic biomarker for patients with GC.
Further mechanical exploration revealed that Fasn knockdown could attenuate Wnt signaling pathway via downregulating distinctive genes, namely Wnt5a, Wnt5b, Fzd2, which at least partly contributed to the decrease in metastasis.
Proteomic profile comparison of the isogenic primary and metastatic colon cancer cell lines SW480 and SW620 identified two potential metastasis related molecular targets: fatty acid synthase and histone H4.
These findings indicate that FASN expression is upregulated in gastric cancer, and increased FASN may be critical to th peritoneal metastasis and survival.
Orlistat is an irreversible inhibitor of FASN activity with cytotoxic properties on several cancer cell lines that inhibits tumor progression and metastasis in prostate cancer xenografts and experimental melanomas, respectively.
Interestingly, pharmacological lipogenesis inhibition with orlistat or fatty acid synthase downregulation with shRNA inhibited tumor regrowth and metastases after sunitinib treatment withdrawal.
These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis.
NPC with high FASN immunoexpression was correlated with advanced pT disease status and worse prognosis in terms of disease-specific survival, metastasis-free survival and local recurrence-free survival, compared to FASN-low group in both univariate and multivariate analyses.
In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease.
Fatty acid synthase (FASN) overexpression has also been associated with a variety of human malignancies including tumor progression, aggressiveness, and metastasis.
This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis.
From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1alpha (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1.