title: The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1.
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.
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Szu-Hua
authors: SH
authors: Pan
authors: Yu-Chih
authors: YC
authors: Chao
authors: Pei-Fang
authors: PF
authors: Hung
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Shuenn-Chen
authors: SC
authors: Yang
authors: Yih-Leong
authors: YL
authors: Chang
authors: Chen-Tu
authors: CT
authors: Wu
authors: Cheng-Chi
authors: CC
authors: Chang
authors: Wen-Lung
authors: WL
authors: Wang
authors: Wing-Kai
authors: WK
authors: Chan
authors: Yi-Ying
authors: YY
authors: Wu
authors: Ting-Fang
authors: TF
authors: Che
authors: Lu-Kai
authors: LK
authors: Wang
authors: Chien-Yu
authors: CY
authors: Lin
authors: Yung-Chie
authors: YC
authors: Lee
authors: Min-Liang
authors: ML
authors: Kuo
authors: Chau-Hwang
authors: CH
authors: Lee
authors: Jeremy J W
authors: JJ
authors: Chen
authors: Tse-Ming
authors: TM
authors: Hong
authors: Pan-Chyr
authors: PC
authors: Yang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D014945:Wound Healing; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D009419:Nerve Tissue Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1; C114864:WASF1 protein, human