Open AccessFER promotes cell migration via regulating JNK activity
Author(s) -
Li Ping,
Ma Zhiwei,
Yu Yun,
Hu Xingjie,
Zhou Yanfeng,
Song Haiyun
Publication year - 2019
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12656
Subject(s) - downregulation and upregulation , cell migration , microbiology and biotechnology , cancer research , kinase , biology , cancer cell , metastasis , signal transduction , regulator , tyrosine kinase , cell , cancer , cell growth , genetics , gene
Objectives Cell migration has a key role in cancer metastasis, which contributes to drug resistance and tumour recurrence. Better understanding of the mechanisms involved in this process will potentially reveal new drug targets for cancer therapy. Fer is a non‐receptor protein tyrosine kinase aberrantly expressed in various human cancers, whereas its role in tumour progression remains elusive. Materials and Methods Transgenic flies and epigenetic analysis were employed to investigate the role of Drosophila Fer (FER) in cell migration and underlying mechanisms. Co‐immunoprecipitation assay was used to monitor the interaction between FER and Drosophila JNK (Bsk). The conservation of Fer in regulating JNK signalling was explored in mammalian cancer and non‐cancer cells. Results Overexpression of FER triggered cell migration and activated JNK signalling in the Drosophila wing disc. Upregulation and downregulation in the basal activity of Bsk exacerbated and eliminated FER‐mediated migration, respectively. In addition, loss of FER blocked signal transduction of the JNK pathway. Specifically, FER interacted with and promoted the activity of Bsk, which required both the kinase domain and the C‐terminal of Bsk. Lastly, Fer regulated JNK activities in mammalian cells. Conclusions Our study reveals FER as a positive regulator of JNK‐mediated cell migration and suggests its potential role as a therapeutic target for cancer metastasis.