1. The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1
- Author
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Min-Liang Kuo, Shuenn Chen Yang, Chen-Tu Wu, Pei Fang Hung, Ting Fang Che, Wen Lung Wang, Yi Ying Wu, Chien-Yu Lin, Szu-Hua Pan, Yung Chie Lee, Wing Kai Chan, Tse-Ming Hong, Chau-Hwang Lee, Yih-Leong Chang, Pan-Chyr Yang, Jeremy J.W. Chen, Hsuan-Yu Chen, Yu Chih Chao, Cheng-Chi Chang, and Lu Kai Wang
- Subjects
Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Nerve Tissue Proteins ,CDC42 ,Biology ,Metastasis ,Mice ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Pseudopodia ,Neoplasm Metastasis ,Lung cancer ,Actin ,Actin nucleation ,Wound Healing ,Cancer ,General Medicine ,medicine.disease ,Wiskott-Aldrich Syndrome Protein Family ,Gene Expression Regulation, Neoplastic ,Cancer cell ,Cancer research ,Dimerization ,Neoplasm Transplantation ,Protein Binding ,Research Article - Abstract
Metastasis is a predominant cause of death in patients with cancer. It is a complex multistep process that needs to be better understood if we are to develop new approaches to managing tumor metastasis. Tumor cell invasion of the local stroma is suppressed by collapsin response mediator protein-1 (CRMP-1). Recently, we identified a long isoform of CRMP-1 (LCRMP-1), expression of which correlates with cancer cell invasiveness and poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). Here, we report that LCRMP-1 overexpression in noninvasive human cell lines enhanced filopodia formation, cancer cell migration, and invasion via stabilization of actin. This effect required a highly conserved N-terminal region of LCRMP-1 as well as the WASP family verprolin-homologous protein-1/actin nucleation pathway (WAVE-1/actin nucleation pathway). Furthermore, LCRMP-1 appeared to act downstream of Cdc42, a Rho family protein known to be involved in actin rearrangement. In addition, LCRMP-1 associated with CRMP-1, which downregulated cancer cell metastasis by interrupting the association of LCRMP-1 and WAVE-1. Finally, we found that high-level expression of LCRMP-1 and low-level expression of CRMP-1 were associated with lymph node metastasis and poor survival in patients with NSCLC. In sum, we show that LCRMP-1 and CRMP-1 have opposing functions in regulating cancer cell invasion and metastasis and propose that this pathway may serve as a potential anticancer target.
- Published
- 2011