Phd in MORPHOGENESIS AND TISSUE ENGINEERING

Thesis title: Myo-Inositol treatment triggers miR-125a-5p expression reducing metastatic potential of breast cancer cells by IP6K1 inhibition

The acquiring of invasive phenotype for metastatic progression is the main cause of death in tumor patients. The investigation about this process in breast cancer patients allowed to identify PI3K/Akt signaling cascade as the main deregulated pathway in Epithelial-Mesenchymal Transition (EMT) process. For long time, PI3K/Akt pathway has been used as target of several drugs. However, toxicity profiles, mutations in specific genes and multiple pathways activated together with PI3K/Akt pathway hamper these drugs from achieving the optimal inhibitory effects making them less attractive for chemoprevention than natural agents such as myo-Inositol. Previously, we demonstrated how myo-Inositol treatment can block EMT in breast cancer cells by downregulating PI3K/Akt and inducing changes in cytoskeletal architecture. Herein, we go insight the mechanism of action of myo-Inositol administration, using as model both triple negative (MDA-MB-231) and hormone responsive (MCF-7) breast cancer cells. Our results suggest that myo-Inositol triggers early modulation in expression pattern, probably led by miRNAs and methylation remodeling of chromatin. The study has allowed us to identify miR-125a-5p and IP6K1 as a novel axis to inhibit motility and metastasis formation using molecular targeted therapies in breast cancer.