Intracellular stiffness is a property of the cancer cells themselves, which, along with ECM invasiveness, plays a significant role in the progression of HCC.<h4>Conclusions</h4>These data suggest that increased intracellular stiffening mirrors increased cell motility and invasive behavior; it can be indicative of suppressed cancer development and progression by the centenarian-associated SIRT6 N308K/A313S mutant. This evidence concerns the gene SIRT6 and hepatocellular carcinoma.