Fat-1 gene inhibits human oral squamous carcinoma cell proliferation through downregulation of β-catenin signaling pathways

Abstract

The ω-3 fatty acid desaturase (fat-1) gene encodes the enzyme that converts ω-6 polyunsaturated fatty acids (PUFAs) to ω-3 PUFAs. Numerous studies have suggested that the ratio of ω-6/ω-3 PUFAs has an impact on tumorigenesis. To investigate the biological function of the fat-1 gene in human oral squamous cell carcinoma (OSCC), the fat-1 gene was introduced into OSCC cells by transfection. The uptake of the gene was confirmed by reverse transcription-polymerase chain reaction and analyzed using gas chromatography. The antitumor effects and mechanisms of the fat-1 gene were evaluated by studying cell survival and tumor growth and. Gas chromatography results revealed that the cells transfected with the fat-1 gene had a higher ω-3/ω-6 PUFA ratio than cells transfected with the control vector. An MTT and DNA fragmentation assay indicated that the presence of the fat-1 gene significantly decreased OSCC cell proliferation and significantly increased the rate of apoptosis. Similar antitumor effects of the fat-1 gene were also observed. Immunohistochemistry analysis confirmed that Tca8113 cell tumors displayed a significant reduction in cell growth and cell survival following the introduction of the fat-1 gene. The current study suggests that the inhibitory effect of the fat-1 gene on tumor growth may be a result of a reduction in the expression of the tumor survival protein β-catenin. The results also support the theory that the ratio of ω-3/ω-6 PUFAs has an impact on OSCC tumor growth. The findings of the study provide notable molecular insight into the theory suggesting that ω-3 PUFAs are an intermediate for the chemoprevention and treatment of human OSCC.

Cadherin Signaling in Cancer: Its Functions and Role as a Therapeutic Target

“…The flamingo cadherin differs from the other cadherins—it has a transmembrane domain that spans the plasma membrane seven times, somewhat like that of G proteins, and participates in many cellular signaling pathways (33) (Figure 1). Fat and dachsous cadherins are very large cell-adhesion molecules (Table 1); a recent study showed the involvement of Fat cadherin in the Wnt-signaling pathway with the help of β-catenin (34) (Figure 1).…”

Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention

“…Furthermore, PUFAs interfere with angiogenesis (VEGF, platelet derived growth factor-PDGF, MMP-2), cell cycle and proliferation (cyclins, p53, phosphate and tensin homolog-PTEN) molecules, all leading to the activation of tumorigenic pathways [79]. More specifically, ω-3 PUFAs have shown to contribute to the chemoprevention of oral cancer, by regulation via β-catenin signaling pathways [185] or via ERK1/2 phosphorylation [186]. In the end, one of the primary sources of lipid molecules is polyunsaturated fatty acids, representing the building blocks of the cell and its processes.…”

Via de sinalização WNT canônica no prognóstico de carcinoma de células escamosas oral

“…On the other hand, FAT1 is involved in the structure and function of the glomerular cleft by podocytes and (Yu et al, 2017), it is important to note that FAT1 is also considered a tumor suppressor gene (Chen et al, 2019). An earlier study reported the loss heterozygosity of FAT1 may be an important factor in the development of astrocytic tumors (Nie et al, 2016).…”