The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1

Szu Hua Pan, Yu Chih Chao, Pei Fang Hung, Hsuan Yu Chen, Shuenn Chen Yang, Yih Leong Chang, Chen Tu Wu, Cheng Chi Chang, Wen Lung Wang, Wing Kai Chan, Yi Ying Wu, Ting Fang Che, Lu Kai Wang, Chien Yu Lin, Yung Chie Lee, Min Liang Kuo, Chau Hwang Lee, Jeremy J.W. Chen, Tse Ming Hong, Pan Chyr Yang

研究成果: Article

47 引文 (Scopus)

摘要

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.

原文English
頁(從 - 到)3189-3205
頁數17
期刊Journal of Clinical Investigation
121
發行號8
DOIs
出版狀態Published - 2011 八月 1

指紋

Pseudopodia
Protein Isoforms
Actins
Neoplasm Metastasis
Neoplasms
Non-Small Cell Lung Carcinoma
Wiskott-Aldrich Syndrome Protein Family
collapsin response mediator protein-1
Cell Movement
Cause of Death
Down-Regulation
Lymph Nodes
Cell Line
Survival

All Science Journal Classification (ASJC) codes

  • Medicine(all)

引用此文

Pan, S. H., Chao, Y. C., Hung, P. F., Chen, H. Y., Yang, S. C., Chang, Y. L., ... Yang, P. C. (2011). The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1. Journal of Clinical Investigation, 121(8), 3189-3205. https://doi.org/10.1172/JCI42975
Pan, Szu Hua ; Chao, Yu Chih ; Hung, Pei Fang ; Chen, Hsuan Yu ; Yang, Shuenn Chen ; Chang, Yih Leong ; Wu, Chen Tu ; Chang, Cheng Chi ; Wang, Wen Lung ; Chan, Wing Kai ; Wu, Yi Ying ; Che, Ting Fang ; Wang, Lu Kai ; Lin, Chien Yu ; Lee, Yung Chie ; Kuo, Min Liang ; Lee, Chau Hwang ; Chen, Jeremy J.W. ; Hong, Tse Ming ; Yang, Pan Chyr. / The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1. 於: Journal of Clinical Investigation. 2011 ; 卷 121, 編號 8. 頁 3189-3205.
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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.",
author = "Pan, {Szu Hua} and Chao, {Yu Chih} and Hung, {Pei Fang} and Chen, {Hsuan Yu} and Yang, {Shuenn Chen} and Chang, {Yih Leong} and Wu, {Chen Tu} and Chang, {Cheng Chi} and Wang, {Wen Lung} and Chan, {Wing Kai} and Wu, {Yi Ying} and Che, {Ting Fang} and Wang, {Lu Kai} and Lin, {Chien Yu} and Lee, {Yung Chie} and Kuo, {Min Liang} and Lee, {Chau Hwang} and Chen, {Jeremy J.W.} and Hong, {Tse Ming} and Yang, {Pan Chyr}",
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Pan, SH, Chao, YC, Hung, PF, Chen, HY, Yang, SC, Chang, YL, Wu, CT, Chang, CC, Wang, WL, Chan, WK, Wu, YY, Che, TF, Wang, LK, Lin, CY, Lee, YC, Kuo, ML, Lee, CH, Chen, JJW, Hong, TM & Yang, PC 2011, 'The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1', Journal of Clinical Investigation, 卷 121, 編號 8, 頁 3189-3205. https://doi.org/10.1172/JCI42975

The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1. / Pan, Szu Hua; Chao, Yu Chih; Hung, Pei Fang; Chen, Hsuan Yu; Yang, Shuenn Chen; Chang, Yih Leong; Wu, Chen Tu; Chang, Cheng Chi; Wang, Wen Lung; Chan, Wing Kai; Wu, Yi Ying; Che, Ting Fang; Wang, Lu Kai; Lin, Chien Yu; Lee, Yung Chie; Kuo, Min Liang; Lee, Chau Hwang; Chen, Jeremy J.W.; Hong, Tse Ming; Yang, Pan Chyr.

於: Journal of Clinical Investigation, 卷 121, 編號 8, 01.08.2011, p. 3189-3205.

研究成果: Article

TY - JOUR

T1 - The ability of LCRMP-1 to promote cancer invasion by enhancing filopodia formation is antagonized by CRMP-1

AU - Pan, Szu Hua

AU - Chao, Yu Chih

AU - Hung, Pei Fang

AU - Chen, Hsuan Yu

AU - Yang, Shuenn Chen

AU - Chang, Yih Leong

AU - Wu, Chen Tu

AU - Chang, Cheng Chi

AU - Wang, Wen Lung

AU - Chan, Wing Kai

AU - Wu, Yi Ying

AU - Che, Ting Fang

AU - Wang, Lu Kai

AU - Lin, Chien Yu

AU - Lee, Yung Chie

AU - Kuo, Min Liang

AU - Lee, Chau Hwang

AU - Chen, Jeremy J.W.

AU - Hong, Tse Ming

AU - Yang, Pan Chyr

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

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U2 - 10.1172/JCI42975

DO - 10.1172/JCI42975

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VL - 121

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JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

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