Conversely, suppression of integrin β1 and Piezo1 all evidently improved ubiquitination level of PFKFB3 protein and reduced the protein expression of PFKFB3 in HCC cells on high‐stiffness substrate (Figure 4C; Figure S4F), further confirming the role of matrix stiffness in PFKFB3 ubiquitination. The gene discussed is PIEZO1; the disease is hepatocellular carcinoma.