Cooperative multi-targeting of signaling networks by angiomiR-204 inhibits vasculogenic mimicry in breast cancer cells.

摘要: Abstract RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach cancer. Here, we uncovered a miR-204 cooperative targeting multiple transducers involved vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration MDA-MB-231 cells leads to potent inhibition reduction number branch points patterned 3D channels. Further analysis activation state using Phosphorylation Antibody Arrays revealed reduced expression phosphorylation levels 13 proteins PI3K/AKT, RAF1/MAPK, VEGF, FAK/SRC signaling. In agreement with phospho-proteomic profiling, was impaired following pharmacological administration PI3K SRC inhibitors. Mechanistic studies confirmed exerts post-transcriptional regulation PI3K-α c-SRC proto-oncogenes. Moreover, overall survival large cohort patients indicates low high were associated worst outcomes. conclusion, our study provides novel lines evidence indicating may fine-tuning synergistic transduction PI3K/AKT/FAK mediators critical formation.