Stretch Induces Invasive Phenotypes in Breast CellsDue to Activation of Aerobic-Glycolysis-Related Pathways

It is increasingly being accepted that cells’ physiological func-tions are substantially dependent to the mechanical character-istics of their surrounding tissue. This is mainly due to the key role of biomechanical forces on cells and their nucleus shapes which have capacity to regulate chromatin conformation and thus gene regulations. Therefore, it is reasonable to postulate that altering the biomechanical properties of a tissue may have capacity to change cell functions. Here, we probed the role of cell stretching (as a model of biomechanical variations) on cell migration and invasion capacity using human breast cells in both normal and cancerous conditions. Using several analy-ses (i.e., scratch assay, invasion to endothelial barrier, real-time RNA sequencing, confocal imaging and patch-clamp etc.) we revealed that cell-stretching process could increase the migra-tion and invasion capabilities of normal and cancerous cells respectively. More specifically, we found that post stretched breast cancer cells had been found in low grades of invasion, substantially upregulate the expression of MnSOD through ac-tivation of H-Ras proteins which subsequently induces aero-bic glycolysis (Warburg effect) followed by overproduction of matrix metalloproteinases (MMP) reinforced filopodias. Pres-ence of such invadopodias facilitate the targeting of vascular endothelial layer and increased invasive behaviors in breast cells are observed.