|Title:||The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1||Authors:||SZU-HUA PAN
|Issue Date:||2011||Journal Volume:||121||Journal Issue:||8||Start page/Pages:||3189-3205||Source:||Journal of Clinical Investigation||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.
|ISSN:||0021-9738||DOI:||10.1172/JCI42975||SDG/Keyword:||actin; peptides and proteins; protein Cdc42; protein crmp 1; protein lcrmp 1; unclassified drug; adult; animal experiment; animal model; animal tissue; article; cancer invasion; cancer survival; cell invasion; cell line; cell migration; cell survival; controlled study; down regulation; human; human cell; human tissue; in vitro study; in vivo study; lung non small cell cancer; lung tumor; lymph node metastasis; major clinical study; male; metastasis; mouse; nonhuman; priority journal; protein expression; protein localization; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Dimerization; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Nerve Tissue Proteins; Protein Binding; Pseudopodia; Wiskott-Aldrich Syndrome Protein Family; Wound Healing
|Appears in Collections:||病理學科所|
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