AKT1 and hepatocellular carcinoma: Recently, our work suggests that higher matrix stiffness significantly attenuates the inhibitory effect of metformin on HCC invasion and metastasis, and PTEN/PI3K/Akt/MMPs pathway contributes to matrix stiffness-mediated metformin resistance [30], highlighting a significant role of biomechanical signal in metformin intervention resistance in HCC.