臺大醫學院-內科;臺大醫學院-病理學科暨研究所;臺大醫學院-基因體暨蛋白體醫學研究所;Wang, Wen-LungWen-LungWangHong, Tse-MingTse-MingHongChang, Yih-LeongYih-LeongChangWu, Chen-TuChen-TuWuPan, Szu-HuaSzu-HuaPanYang, Pan-ChyrPan-ChyrYang2014-02-142018-07-112014-02-142018-07-112012http://ntur.lib.ntu.edu.tw//handle/246246/259771LCRMP-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 GSK3 beta 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 GSK3 beta diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3 beta expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3 beta expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3 beta-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome.110 bytestext/html[SDGs]SDG3http://ntur.lib.ntu.edu.tw/bitstream/246246/259771/1/index.html