Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers.
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 time-dependent 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.
Yeh
Ching-Sheng
CS
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC.
Wang
Jaw-Yuan
JY
Chung
Fu-Yen
FY
Lee
Su-Chen
SC
Huang
Ming-Yii
MY
Kuo
Chia-Wei
CW
Yang
Ming-Je
MJ
Lin
Shiu-Ru
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D000071063:Endoglin; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D051272:Glucose Transporter Type 1; D007527:Isoenzymes; D011956:Receptors, Cell Surface; C495677:SLC2A1 protein, human; D003847:Deoxyglucose; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C472074:HK1 protein, human; D006593:Hexokinase; D010735:Phosphoglycerate Kinase; C104317:phosphoglycerate kinase, testis specific; D005947:Glucose