Acquisition of Invasiveness by Breast Adenocarcinoma Cells Engages Established Hallmarks and Novel Regulatory Mechanisms.

ABSTRACT

BACKGROUND/AIM: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. MATERIALS AND METHODS: Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. RESULTS: We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive re-arrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. CONCLUSION: Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation.