Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers

Abstract

Abstract. We investigated gene expressions involved in the glycolytic pathways in colorectal cancer. The study was designed to use gene ontology and its relevant bioinformatics tools to analyze the microarray data obtained from CRC tissues and their corresponding normal tissues, in order to explore the correlation between the glycolytic metabolic pathway and possible pathogenesis of this disease. The overexpression of glycolysis-related genes was observed in over 76% of CRC tissues. In addition, we stimulated the SW480 and SW620 CRC cell lines with 15 mM D-(+)-glucose and 10 mM 2-deoxy-D-glucose respectively. The results indicate that the proliferation response of both the SW480 and SW620 cell lines increased remarkably with a time-dependent effect by D-(+)-glucose administration. In contrast, the proliferation response of both the SW480 and SW620 cell lines was significantly inhibited by 2-DG administration. Likewise, further analyses of the expression of related genes triggered by the D-(+)-glucose in vivo show that the activation process of these eight genes -GLUT1, HK1, GPI, GAPD, PGK1, PGK2, ENO2, PKM2 -prominently increased with a timedependent effect. In conclusion, this study demonstrates that the glycolytic pathway and glycolysis-related genes may play an important role in the tumorigenesis of CRC, but their molecular mechanisms need further investigation to verify this.

Pyruvate uptake is increased in highly invasive ovarian cancer cells under anoikis conditions for anaplerosis, mitochondrial function, and migration

“…These include hexokinase and phosphofructokinase-1, which control conversion of glucose to glucose 6-phosphate and conversion of fructose 6-phosphate to fructose 1,6-bisphosphate, respectively (19). Genes for enzymes involved in the glycolytic pathway have also been seen to be overexpressed in several studies (2,38). Tumor suppressor p53 has also been shown to be involved in increasing rates of glycolysis in cancer cells compared with normal cells (21,39), as well as HIF-1␣ (15,39).…”

PGK1 a Potential Marker for Peritoneal Dissemination in Gastric Cancer

“…Right: Heatmap of the 100 genes clustered using k-means (with k=2). how PGK1 advances migration, adhesion and growth control is yet unclear, it is recognized that enhanced glycolytic metabolism will provide more energy (ATP) for cell proliferation and growth and will increase the concentration of metabolites such as lactate and pyruvate to regulate hypoxia-inducible gene expression and actuate the expression of CXCR4, its ligand CXCL12 and the downstream effector of Wnt signalling β-catenin that are known to be involved in migration, adhesion and growth [10,14,[25][26][27].…”

Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line

“…Обна-ружено (Funasaka et al, 2005), что в условиях гипоксии наблюдается повышение экспрессии гена GPI в клеточных линиях рака молочной железы (BT-549), а ингибирование его экспрессии приводит к снижению подвижности опухо-левых клеток. При стимуляции гликолиза D-(+)-глюкозой в клеточных линиях КРР (SW480 и SW620) отмечено по-вышение экспрессии гена GPI и, наоборот, при обработке клеток ингибитором гликолиза 2-дезокси-D-глюкозой (2-DG) экспрессия GPI снижалась (Yeh et al, 2008). Нами выявлено значительное подавление экспрессии гена GPI в условиях ингибирования HK2.…”