Open AccessMICAL‐L2 potentiates Cdc42‐dependent EGFR stability and promotes gastric cancer cell migration
Author(s) -
Min Pengxiang,
Zhao Shuo,
Liu Lei,
Zhang Yujie,
Ma Yadong,
Zhao Xuyang,
Wang Yueyuan,
Song Yixuan,
Zhu Chenchen,
Jiang Haonan,
Gu Luo,
Du Jun
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14353
Subject(s) - cdc42 , gene silencing , cancer research , rac1 , epidermal growth factor receptor , cell migration , microbiology and biotechnology , cancer cell , biology , cancer , cell , chemistry , signal transduction , gene , biochemistry , genetics
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/β‐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.