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

Oncogene volume 29, pages 4555–4566 (2010)Cite this article

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Abstract

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.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

2D:

two-dimensional

BPH:

benign prostate hyperplasia

CRMP:

collapsin response mediator protein

DIGE:

fluorescence difference gel electrophoresis

EGFP:

enhanced green fluorescent protein

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

IHC:

immunohistochemistry

LNM:

lymph node metastasis

MSP:

methylation specific PCR

PCa:

prostate cancer

VEGF:

vascular endothelial growth factor

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Acknowledgements

We thank Professor Quentin Liu (State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University) for providing excellent technical assistances. Special thanks to Professor Zhou Zhu (Johns Hopkins University, School of Medicine, USA) for valuable suggestions and critical reading of this paper. This work was supported by Chinese National Natural Science Foundation 30772178, 30973011, 30901496, Key Project of Guangdong Provincial Science and Technology Research 7117362, Key Project of Chinese Ministry of Health and Chinese National Hi-Tech Research and Development Program 2007AA021906.

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  1. X Gao, J Pang and L-Y Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    X Gao, J Pang, L-Y Li, W-P Liu, J-M Di, Q-P Sun, Y-Q Fang, X-P Liu & X-Y Pu

  2. Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    D He & Z-L Su

  3. Proteomics Center, Zhongshan School of Medcine, Sun Yat-sen University, Guangzhou, China

    M-T Li

  4. Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA

    B-Y Li

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Correspondence to X Gao.

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Gao, X., Pang, J., Li, LY. et al. Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer. Oncogene 29, 4555–4566 (2010). https://doi.org/10.1038/onc.2010.213

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