Phosphorylation of LCRMP-1 by GSK3β promotes filopoda formation, migration and invasion abilities in lung cancer cells

Wen Lung Wang, Tse-Ming Hong, Yih Leong Chang, Chen Tu Wu, Szu Hua Pan, Pan Chyr Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion and associate with poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in cancer cell invasiveness still remain obscure. Here, we report that GSK3β can phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation is crucial for function of LCRMP-1 to promote filopodia formation, migration and invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion abilities in cancer cells; simultaneously, kinase-dead GSK3β diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3β expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3β expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3β-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome.

Original languageEnglish
Article numbere31689
JournalPloS one
Volume7
Issue number2
DOIs
Publication statusPublished - 2012 Feb 21

Fingerprint

Phosphorylation
lung neoplasms
Lung Neoplasms
phosphorylation
Cells
pseudopodia
Neoplasms
Pseudopodia
cell invasion
consensus sequence
Consensus Sequence
cell movement
Non-Small Cell Lung Carcinoma
Cell Movement
neoplasm cells
Protein Isoforms
phosphotransferases (kinases)
Phosphotransferases
Survival

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wang, Wen Lung ; Hong, Tse-Ming ; Chang, Yih Leong ; Wu, Chen Tu ; Pan, Szu Hua ; Yang, Pan Chyr. / Phosphorylation of LCRMP-1 by GSK3β promotes filopoda formation, migration and invasion abilities in lung cancer cells. In: PloS one. 2012 ; Vol. 7, No. 2.
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abstract = "LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion and associate with poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in cancer cell invasiveness still remain obscure. Here, we report that GSK3β can phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation is crucial for function of LCRMP-1 to promote filopodia formation, migration and invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion abilities in cancer cells; simultaneously, kinase-dead GSK3β diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3β expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3β expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3β-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome.",
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Phosphorylation of LCRMP-1 by GSK3β promotes filopoda formation, migration and invasion abilities in lung cancer cells. / Wang, Wen Lung; Hong, Tse-Ming; Chang, Yih Leong; Wu, Chen Tu; Pan, Szu Hua; Yang, Pan Chyr.

In: PloS one, Vol. 7, No. 2, e31689, 21.02.2012.

Research output: Contribution to journalArticle

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AU - Pan, Szu Hua

AU - Yang, Pan Chyr

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