Open AccessMICAL 1 facilitates breast cancer cell proliferation via ROS ‐sensitive ERK /cyclin D pathway
Author(s) -
Deng Wenjie,
Wang Yueyuan,
Zhao Shuo,
Zhang Yujie,
Chen Yan,
Zhao Xuyang,
Liu Lei,
Sun Shixiu,
Zhang Lin,
Ye Bixing,
Du Jun
Publication year - 2018
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.13588
Subject(s) - cyclin d , mapk/erk pathway , wnt signaling pathway , cyclin dependent kinase , cyclin d1 , cell growth , protein kinase b , kinase , biology , cancer research , pi3k/akt/mtor pathway , microbiology and biotechnology , cell cycle , signal transduction , chemistry , cell , biochemistry
Abstract Molecule interacting with CasL 1 ( MICAL 1) is a multidomain flavoprotein mono‐oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL 1 modulates reactive oxygen species ( ROS ) production, and the latter then activates phosphatidyl inositol 3‐kinase ( PI 3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL 1 in breast cancer cell proliferation and to explore the potential molecular mechanism. We noticed that depletion of MICAL 1 markedly reduced cell proliferation in breast cancer cell line MCF ‐7 and T47D. This effect of MICAL 1 on proliferation was independent of wnt/β‐catenin and NF ‐κB pathways. Interestingly, depletion of MICAL 1 significantly inhibited ROS production, decreased p‐ ERK expression and unfavourable for proliferative phenotype of breast cancer cells. Likewise, MICAL 1 overexpression increased p‐ ERK level as well as p‐ ERK nucleus translocation. Moreover, we investigated the effect of MICAL 1 on cell cycle‐related proteins. MICAL 1 positively regulated CDK 4 and cyclin D expression, but not CDK 2, CDK 6, cyclin A and cyclin E. In addition, more expression of CDK 4 and cyclin D by MICAL 1 overexpression was blocked by PI 3K/Akt inhibitor LY 294002. LY 294002 treatment also attenuated the increase in the p‐ ERK level in MICAL 1‐overexpressed breast cancer cells. Together, our results suggest that MICAL 1 exhibits its effect on proliferation via maintaining cyclin D expression through ROS ‐sensitive PI 3K/Akt/ ERK signalling in breast cancer cells.