![extracellular matrix extracellular matrix](https://www.researchgate.net/publication/337790751/figure/fig1/AS:833100485509123@1575638042764/A-The-extracellular-matrix-ECM-secretion-depends-mainly-on-cancer-associated.png)
![extracellular matrix extracellular matrix](https://www.mdpi.com/materials/materials-12-01311/article_deploy/html/images/materials-12-01311-g001.png)
ConclusionĪ higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. Our purpose was to explore the role of matrix stiffness in liver cancer development. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Cancer development is strictly correlated to composition and physical properties of the extracellular matrix.