MICAL1 controls cell invasive phenotype via regulating oxidative stress in breast cancer cells

作者：Wenjie Deng, Yueyuan Wang, Luo Gu, Biao Duan, Jie Cui, Yujie Zhang, Yan Chen, Shixiu Sun, Jing Dong, Jun Du · 发表于：BMC Cancer · 年份：2016 · DOI：10.1186/s12885-016-2553-1 · 被引用次数：87 · 研究领域：Axon Guidance and Neuronal Signaling、Apelin-related biomedical research、Sirtuins and Resveratrol in Medicine

BACKGROUND: Molecules Interacting with CasL (MICAL1), a multidomain flavoprotein monoxygenase, is strongly involved in the mechanisms that promote cancer cell proliferation and survival. Activation of MICAL1 causes an up-regulation of reactive oxygen species (ROS) in HeLa cells. ROS can function as a signaling molecule that modulates protein phosphorylation, leading to malignant phenotypes of cancer cells such as invasion and metastasis. Herein, we tested whether MICAL1 could control cell migration and invasion through regulating ROS in breast cancer cell lines. METHODS: The effects of depletion/overexperssion of MICAL1 on cell invasion rate were measured by matrigel-based transwell assays. The contents of ROS in breast cancer cells were evaluated by CM2-DCFHDA staining and enhanced lucigenin chemiluminescence method. RAB35 activity was assessed by pulldown assay. The relationship of RAB35 and MICAL1 was evaluated by immunofluorescence, coimmunoprecipitation, immunoblotting and co-transfection techniques. Immunoblotting assays were also used to analyze Akt phosphorylation level. RESULTS: In this study, we found that depletion of MICAL1 reduced cell migration and invasion as well as ROS generation. Phosphorylation of Akt was also attenuated by MICAL1 depletion. Likewise, the over-expression of MICAL1 augmented the generation of ROS, increased Akt phosphorylation, and favored invasive phenotype of breast cancer cells. Moreover, we investigated the effect of EGF signaling on MIC...