RESUMEN
PURPOSE: Lung cancer is the leading cause of cancer-related mortalities worldwide, and metastasis contributes to a large number of deaths in lung carcinoma patients. New approaches for anti-metastatic treatment are urgently needed. Enhanced fructose metabolism mediated by GLUT5 directly contributes to cancer metastasis. However, the underlying mechanism remains to be elucidated, which we aimed to explore in this study. METHODS: The overexpression and knockdown of SLC2A5, the encoding gene of GLUT5, were established by retrovirus system and CRISPR/Cas9 technology, respectively. Cell migration was conducted by trans-well assay. Western blotting assay was carried out to detect the expression of GLUT5, total AKT, phosphorylated AKT (pAKT-S473 and pAKT-T308) and LDHA. Lactate production was measured by colorimetric assay. Experimental lung metastasis model by tail vein injection was constructed to evaluate the metastatic potential of GLUT5 in vivo. RESULTS: Overexpression of SLC2A5 promoted migration of lung cancer cells both in vitro and in vivo, and shortened the overall survival of mice. While, SLC2A5 deletion blocked the migration of lung cancer cells. GLUT5-mediated fructose utilization upregulated phosphorylated AKT, which was responsible for enhanced migration of lung cancer cells. Additionally, GLUT5-mediated fructose utilization boosted glycolysis with overproduction of lactate, resulting in upregulation of phosphorylated AKT. Moreover, lung cancer cell migration and AKT activation were restrained by glycolysis inhibitor 2-deoxy-D-glucose (2-DG) or GLUT5-specific inhibitor 2,5-anhydro-D-mannitol (2,5-AM). CONCLUSION: Our study unveils glycolysis/lactate/AKT pathway is responsible for lung cancer cell migration induced by GLUT5-mediated fructose metabolism, providing a potential therapeutic avenue for lung cancer metastasis.
Asunto(s)
Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Movimiento Celular , Fructosa/metabolismo , Fructosa/farmacología , Glucólisis , Lactatos , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Background: Finding molecular markers linked to quantitative trait loci is the first step in marker-assisted selection (MAS). Microsatellites are excellent molecular markers because of their large numbers, even distribution in the genome, and high polymorphism. In this study, the polymerisation effect of four microsatellites (OarAE101, BM1329, BM143, and LSCV043) on litter size was analysed using microsatellite markers and pedigrees. Results: The results indicate that the polymerisation effect of four microsatellite loci significantly affected the litter size. E5E10F2F6G1G5H6H11 and E3E8F5F7G1G5H3H9 had the highest and lowest litter sizes in the F2 generation, respectively. The polymerisation effect value (v) of the E5E10 genotype was 3.18% higher than that of the E2E7 genotype. The v of genotype F2F6 was 14.47% higher than that of the F5F7 genotype. The v of genotype G1G5 was 58.99% higher than that of the G2G7 genotype. The v of the H6H11 genotype was 5.60% to 49.74% higher than those of the H4H10 and H1H7 genotypes. The v of the H3H9 genotype was 17.22% higher than that of the H1H7 genotype. Conclusions: The results of the present study are vital to improving the reproductive performance in goat breeds MAS.