MICAL1 facilitates breast cancer cell proliferation via ROS‐sensitive ERK/cyclin D pathway
Open Access
- 10 March 2018
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 22 (6), 3108-3118
- https://doi.org/10.1111/jcmm.13588
Abstract
Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono-oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism. We noticed that depletion of MICAL1 markedly reduced cell proliferation in breast cancer cell line MCF-7 and T47D. This effect of MICAL1 on proliferation was independent of wnt/β-catenin and NF-κB pathways. Interestingly, depletion of MICAL1 significantly inhibited ROS production, decreased p-ERK expression and unfavourable for proliferative phenotype of breast cancer cells. Likewise, MICAL1 overexpression increased p-ERK level as well as p-ERK nucleus translocation. Moreover, we investigated the effect of MICAL1 on cell cycle-related proteins. MICAL1 positively regulated CDK4 and cyclin D expression, but not CDK2, CDK6, cyclin A and cyclin E. In addition, more expression of CDK4 and cyclin D by MICAL1 overexpression was blocked by PI3K/Akt inhibitor LY294002. LY294002 treatment also attenuated the increase in the p-ERK level in MICAL1-overexpressed breast cancer cells. Together, our results suggest that MICAL1 exhibits its effect on proliferation via maintaining cyclin D expression through ROS-sensitive PI3K/Akt/ERK signalling in breast cancer cells.Keywords
Funding Information
- National Natural Science Foundation of China (81773107, 81602561, 81372319)
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