I developed a novel method to correlate single-cell mechanical properties (such as stiffness and viscosity) with gene expression, enabling direct analysis of how mechanotype relates to genotype. Using this approach, I identified correlations between cell stiffness and genes implicated in extracellular matrix remodeling (TGM2), epithelial-to-mesenchymal transition (VIM, ZEB1, CDH1), nuclear structure (LMNA), and metastasis suppressors (TIMP3). I also discovered a set of regulatory “control node” genes – including miR183 and CD82 – whose perturbation can predictably alter both cell mechanics and invasive potential. These findings represent a critical step toward uncovering the molecular mechanisms governing cell mechanics and how they can be targeted to modulate cancer cell behavior.