MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration
MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration
复制标题
MICAL-L2 增强 Cdc42 依赖性 EGFR 稳定性并促进胃癌细胞迁移
DOI：
10.1111/jcmm.14353
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发表时间：
2019-06-01
影响因子：
5.3
通讯作者：
Du, Jun
中科院分区：
文献类型：
--
作者：
Min, Pengxiang;Zhao, Shuo;Du, Jun
Enhanced migration potential is a common characteristic of cancer cells induced by mechanisms that are incompletely defined. The present study was designed to investigate relationship of a new discovered cytoskeleton regulator MICAL-L2 and the endogenous epidermal growth factor receptor (EGFR) signalling pathways in gastric cancer cell migration. Increased expression of MICAL-L2 in gastric cancer cells up-regulated EGFR protein level, accompanied by the increase of cell migration, whereas silencing MICAL-L2 down-regulated EGFR and inhibited cell migration. Expression of MICAL-L2 was also shown positively correlated with the activation of HSP27/cytoskeleton and HSP27/beta-catenin signalling pathways that provide key mechanisms controlling cell migration. The up-regulating effect of MICAL-L2 on EGFR is mediated through a transcription-independent mechanism that involves inhibiting EGFR protein degradation in lysosome. Further analysis indicated that Cdc42 activation contributed in maintaining the effect of MICAL-L2 on EGFR stability. Furthermore analysis of clinic specimens revealed increased expression of MICAL-L2 in carcinoma tissues and a positive correlation between MICAL-L2 and EGFR expression levels. The above results indicate that MICAL-L2 potentiates gastric cell migration via inhibiting EGFR degradation in lysosome via a Cdc42-dependent manner that leads to the activation of EGFR/HSP27 signalling pathways.
