Abstract
BackgroundWe have identified an environmentally inducible gene, mdig that predicted the overall survival in breast cancer patients. We showed that mdig regulated breast cancer cell growth, motility and invasion partially through DNA and histone methylation. However, we have lacked a comprehensive analysis of the proteomic profile of mdig in triple negative breast cancer cells. MethodsWe applied mass spectrometry to acquire global proteomic and post translational modification analysis for triple negative breast cancer cells MDA-MB-231 that had mdig deleted via CRISPR Cas 9 gene editing. Using label-free bottom up quantitative proteomics, we compared wildtype control (WT) and mdig knockout (KO) MDA-MB-231 cells and identified the proteins and pathways that are significantly altered with mdig deletion. The Ingenuity Pathway Analysis (IPA) platform was further used to explore the signaling pathway networks incorporating differentially expressed proteins. Results904 differentially expressed (p < 0.005) proteins were identified in MDA-MB-231 cells that had mdig deletion. Approximately 30 pathways and networks linked to the pathogenicity of breast cancer and populated by the differentially expressed proteins were either activated or inhibited. IPA established that the differentially expressed proteins have relevant biological actions in cell growth, motility and malignancy. This analysis provides a rich source of potential candidate therapeutic targets with potential prognostic significance in triple negative breast cancer. Data are available via ProteomeXchange with identifier PXD016688.Conclusions These data provide the first insight into protein expression patterns in breast cancer associated with a complete disruption of the mdig gene. Differentially expressed proteins between WT and KO MDA-MB-231 triple negative breast cancer cells provide substantial information regarding key proteins, biological process and pathways that are modulated by mdig and contribute to breast cancer tumorigenicity and invasiveness. Mdig modulated signaling pathways and hub molecules provide novel targets for the development of treatment strategies and breast cancer therapies.
Co-Targeting IGF-1R and Autophagy Enhances the Effects of Cell Growth Suppression and Apoptosis Induced by the IGF-1R Inhibitor NVP-AEW541 in Triple-Negative Breast Cancer Cells
