Phosphorylation of LCRMP-1 by GSK3β promotes filopoda formation, migration and invasion abilities in lung cancer cells
Journal
PLoS ONE
Journal Volume
7
Journal Issue
2
Pages
e31689
Date Issued
2012
Author(s)
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. ? 2012 Wang et al.
SDGs
Other Subjects
glycogen synthase kinase 3beta; long form collapsin response mediator protein 1; oncoprotein; unclassified drug; CRMP1 protein, human; glycogen synthase kinase 3; glycogen synthase kinase 3 beta; isoprotein; nerve protein; phosphothreonine; amino terminal sequence; article; cancer cell; cancer staging; carboxy terminal sequence; cell invasion; cell migration; controlled study; enzyme inactivation; female; filopodium; human; human cell; human tissue; lung cancer; major clinical study; male; nucleotide sequence; overall survival; protein expression; protein function; protein localization; protein motif; protein phosphorylation; sequence alignment; site directed mutagenesis; tumor volume; amino acid sequence; cancer invasion; cell motion; chemistry; enzyme activation; enzyme specificity; enzymology; Kaplan Meier method; lung non small cell cancer; lung tumor; metabolism; middle aged; molecular genetics; pathology; phosphorylation; proportional hazards model; pseudopodium; tumor cell line; Amino Acid Sequence; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Enzyme Activation; Glycogen Synthase Kinase 3; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Molecular Sequence Data; Neoplasm Invasiveness; Nerve Tissue Proteins; Phosphorylation; Phosphothreonine; Proportional Hazards Models; Protein Isoforms; Pseudopodia; Substrate Specificity
Type
journal article