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.
References
Dec 21, 1995·Nature·D A CrossB A Hemmings
Oct 6, 1997·American Journal of Respiratory Cell and Molecular Biology·Y W ChuC W Wu
Sep 20, 2001·Journal of the National Cancer Institute·J Y ShihP C Yang
Sep 21, 2001·The Biochemical Journal·S Frame, P Cohen
Mar 7, 2002·Trends in Molecular Medicine·Hagit Eldar-Finkelman
Apr 17, 2002·Cell·Chunming LiuXi He
Jul 13, 2002·Journal of Surgical Oncology·Frederick L Greene, Leslie H Sobin
Jan 2, 2003·Nature Reviews. Cancer·Patricia S Steeg
Feb 26, 2003·Cell·Thomas D Pollard, Gary G Borisy
Mar 5, 2003·Journal of Cell Science·Bradley W Doble, James R Woodgett
Mar 26, 2003·Clinical & Experimental Metastasis·Jin-Yuan ShihPan-Chyr Yang
Nov 19, 2003·The Journal of Cell Biology·Maralice Conacci-SorrellAvri Ben-Ze'ev
Dec 10, 2003·Neuroreport·Gautam N Bijur, Richard S Jope
Sep 17, 2004·Genes & Development·Felix H BrembeckWalter Birchmeier
Sep 28, 2004·Nature Cell Biology·Binhua P ZhouMien-Chie Hung
Oct 7, 2004·The Journal of Biological Chemistry·Adam R ColeCalum Sutherland
Jan 18, 2005·Cell·Takeshi YoshimuraKozo Kaibuchi
Mar 16, 2006·Molecular and Cellular Biology·Xinming CaiMichael D Schaller
Aug 8, 2006·Nature Medicine·Patricia S Steeg
Jul 9, 2008·Cancer Letters·Jia Luo
Sep 13, 2008·American Journal of Respiratory and Critical Care Medicine·Yu-Chih ChaoPan-Chyr Yang
Apr 14, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Szu-Hua PanPan-Chyr Yang
Nov 12, 2009·Cancer Research·Joydeep MukherjeeAbhijit Guha
Jul 13, 2011·The Journal of Clinical Investigation·Szu-Hua PanPan-Chyr Yang
Citations
Apr 8, 2015·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Jiyeon YoonByung Lan Lee
Apr 5, 2017·Cancer Medicine·Lin WangJunqiang Yin
Jan 27, 2017·Anti-cancer Drugs·Zhongping ZhouJian Lu
Apr 26, 2014·Oncology Letters·Fei TanZhijie Li
Dec 22, 2016·Oncotarget·James A McCubreyMassimo Libra
Oct 24, 2014·International Journal of Oncology·Wei ZhouLimin Rong
Jun 28, 2016·Oncology Letters·Huige HouSongwei Xun
Aug 28, 2021·Cells·Daria HajkaAgnieszka Gizak