Open AccessBHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway
Author(s) -
Zhang Di,
Zheng Qin,
Wang Chen,
Zhao Na,
Liu Yang,
Wang Enhua
Publication year - 2020
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.15033
Subject(s) - gene silencing , mapk/erk pathway , microbiology and biotechnology , signal transduction , cell , biology , cell growth , chemistry , cancer research , biochemistry , gene
Abstract Deregulation of the basic helix‐loop‐helix family member e41 (BHLHE41) has been characterized as a marker of progression of several cancers. In this study, we aimed to explore the mechanism by which BHLHE41 regulates the invasion of breast cancer cells. BHLHE41 suppresses, whereas the silencing of BHLHE41 promotes tumour invasion of both MCF‐7 and MDA‐MB‐231 cells. Meanwhile, BHLHE41 down‐regulated the transcription and translation of SNAI1, SNAI2, VIM and CDH2, and up‐regulated those of CLDN1, CLDN4 and CDH1. Reporter assay indicated that silencing of BHLHE41 dramatically activated the MAPK/JNK signalling pathway in MCF‐7 cell line and the hypoxia signalling pathway in MDA‐MB‐231 cell line. Furthermore, silencing of BHLHE41 activated the MAPK/JNK signalling pathway by up‐regulating phosphorylated JNK and failed to affect the expression of HIF‐1 alpha in MCF‐7 cells. After blocking the MAPK/JNK signalling pathway by specific inhibitor SP600125, silencing of BHLHE41 failed to promote tumour cell invasion. These results suggest that BHLHE41 facilitates MCF‐7 cell invasion mainly via the activation of MAPK/JNK signalling pathway. In conclusion, although BHLHE41 suppresses tumour invasion in MCF‐7 and MDA‐MB‐231 cell lines, the specific regulatory mechanisms may be different.