Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer

• Published in: Oncogene Vol. 29; no. 32; pp. 4555 - 4566
• Main Authors: Gao, X, Pang, J, Li, L-Y, Liu, W-P, Di, J-M, Sun, Q-P, Fang, Y-Q, Liu, X-P, Pu, X-Y, He, D, Li, M-T, Su, Z-L, Li, B-Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.08.2010; Nature Publishing Group
• Subjects: 631/337/475; 631/67/322; 631/67/589/466; Animal models; Animals; Apoptosis; Biological and medical sciences; Care and treatment; Cell Biology; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular proteins; CpG islands; CpG Islands - genetics; Development and progression; DNA Methylation; Electrophoresis, Gel, Two-Dimensional; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetics; Gynecology. Andrology. Obstetrics; Health aspects; Human Genetics; Humans; Internal Medicine; Lymph nodes; Lymphatic Metastasis; Male; Male genital diseases; Mediator protein; Medical sciences; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Molecular and cellular biology; Mortality; Muscle Proteins - genetics; Muscle Proteins - metabolism; Nephrology. Urinary tract diseases; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oncology; original-article; Promoter Regions, Genetic - genetics; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Proteomics; Recurrence; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vascular Endothelial Growth Factor A - metabolism; United States; China; prostate cancer; proteomics; collapsin response mediator protein-4; methylation; metastasis-suppressor gene; Urinary system disease; Prostate disease; Identification; Malignant tumor; Metastasis; Carcinogenesis; Protein; Gene expression profile; Metastasis suppressor gene; Proteomics; Methylation; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.213

Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasis-suppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer.