Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis.
Colorectal cancer is the second leading killer cancer worldwide and presently the most common cancer among males in Singapore. The study aimed to detect changes of protein profiles associated with the process of colorectal tumorigenesis to identify specific protein markers for early colorectal cancer detection and diagnosis or as potential therapeutic targets. Seven pairs of colorectal cancer tissues and adjacent normal mucosa were examined by two-dimensional gel electrophoresis at basic pH range (pH 7-10). Intensity changes of 34 spots were detected with statistical significance. 16 of the 34 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. Changes in protein expression levels revealed a significantly enhanced glycolytic pathway (Warburg effect), a decreased gluconeogenesis, a suppressed glucuronic acid pathway, and an impaired tricarboxylic acid cycle. Observed changes in protein abundance were verified by two-dimensional DIGE. These changes reveal an underlying mechanism of colorectal tumorigenesis in which the roles of impaired tricarboxylic acid cycle and the Warburg effect may be critical.
Department of Biological Sciences, National University of Singapore, Singapore 117543.
Xuezhi
X
Bi
Qingsong
Q
Lin
Tet Wei
TW
Foo
Shashikant
S
Joshi
Tao
T
You
Han-Ming
HM
Shen
Choon Nam
CN
Ong
Peh Yean
PY
Cheah
Kong Weng
KW
Eu
Choy-Leong
CL
Hew
D016022:Case-Control Studies; D002952:Citric Acid Cycle / Q000235:genetics; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis / Q000235:genetics; D005965:Glucuronates / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D040901:Proteomics; D012846:Singapore; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation
D005965:Glucuronates