Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells

Jin Yuan Shih, Shuenn Chen Yang, Tse Ming Hong, Ang Yuan, Jeremy J.W. Chen, Chong Jen Yu, Yih Leong Chang, Yung Chie Lee, Konan Peck, Cheng-Wen Wu Lee, Pan Chyr Yang*

*Corresponding author for this work

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Background: Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL1-0, CL1-1, CL1-5, and CL1-5-F4 in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize. Methods: We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL1-5 cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). All statistical tests were two-sided. Results: Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL1-5 cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P<.001). During interphase, CRMP-1 protein was present uniformly throughout the cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was associated with mitotic spindles, centrosomes, and the midbody (in late telophase). Real-time RT-PCR of lung cancer specimens showed that reduced expression of CRMP-1 was statistically significantly associated with advanced disease (stage III or IV; P = .010), lymph node metastasis (N1, N2, and N3; P = .043), early postoperative relapse (P = .030), and shorter survival (P = .016). Conclusions: CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion-suppressor gene.

Original languageEnglish
Pages (from-to)1392-1400
Number of pages9
JournalJournal of the National Cancer Institute
Volume93
Issue number18
DOIs
StatePublished - 19 Sep 2001

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    Shih, J. Y., Yang, S. C., Hong, T. M., Yuan, A., Chen, J. J. W., Yu, C. J., Chang, Y. L., Lee, Y. C., Peck, K., Wu Lee, C-W., & Yang, P. C. (2001). Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells. Journal of the National Cancer Institute, 93(18), 1392-1400. https://doi.org/10.1093/jnci/93.18.1392