Proteomic-based identification of the APC-binding protein EB1 as a candidate of novel tissue biomarker and therapeutic target for colorectal cancer.
Novel candidates of biomarker and therapeutic target in colorectal cancer (CRC) were investigated using a proteomic approach. The proteome of normal colorectal epithelial tissues was compared with that of the tumor ones in 59 CRC patients using two-dimensional difference gel electrophoresis. Of 3458 protein spots, 110 exhibited statistically significant (p<0.01) differences in intensity (more than 2.5-folds) between the normal and tumor tissue groups. Of 67 unique gene products that were identified for 105 of the 110 protein spots, we focused on the higher expression of the adenoma polyposis coli-binding protein EB1 (EB1). EB1 was originally discovered as a binding protein of APC, which is a tumor suppressor gene product, and the expression of EB1 has been associated with poor prognosis in several malignancies but not in CRC. Immunohistochemical analysis of the 132 CRC cases revealed that EB1 was overexpressed in tumor cells in correlation with poor prognosis. Suppression of EB1 by RNAi inhibited CRC cell proliferation and invasion. In this study, the overexpression of EB1 in CRC tissues correlating with prognosis, and its functional contribution to the malignant phenotypes of CRC cells are described. The present findings indicate that EB1 is a potential biomarker and therapeutic target in CRC.
Division of Pharmacoproteomics, National Cancer Center Research Institute, Japan.
Yutaka
Y
Sugihara
Hirokazu
H
Taniguchi
Ryoji
R
Kushima
Hitoshi
H
Tsuda
Daisuke
D
Kubota
Hiroshi
H
Ichikawa
Kano
K
Sakamoto
Yukiko
Y
Nakamura
Takeshi
T
Tomonaga
Shin
S
Fujita
Tadashi
T
Kondo
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000368:Aged; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D055808:Drug Discovery; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D040901:Proteomics / Q000379:methods
C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins