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Oncology - Pathology - Public Health and Epidemiology


Phosphorylation of LCRMP-1 by GSK3ß Promotes Filopoda Formation, Migration and Invasion Abilities in Lung Cancer Cells
Published: Tuesday, February 21, 2012
Author: Wen-Lung Wang et al.

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

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 GSK3ß 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 GSK3ß diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3ß expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3ß expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3ß-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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