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               ·942 ·                            南 京    医 科 大 学 学         报                        2025年7月


              A                                                             B    150
                                                                                         P < 0.01
                                                   Relative CNN2 protein expression  1.0  Relative migration cells

                      Hard       Normal             2.5     P < 0.01            (%)  100    P < 0.001
                                                    2.0
              CNN2                        13 kDa    1.5


              Tublin                      55 kDa    0.5                           50


                                                      0
                                                          Hard  Normal
                                                                                   0
                                                                                       Hard  Normal  Hard⁃shCNN2
                 A:Western blot analysis showed that the protein expression of CNN2 in liver cancer cells cultured on rigid substrates was higher than that in
              normal culture medium. B:Both rigid substrates and CNN2 promote migration(n=3).
                                          图4 ECM力学信号调控CNN2促进肝癌细胞迁移
                            Figure 4 ECM mechanical signals regulate CNN2 to promote liver cancer cell migration

              A                       B
                         Huh⁃7
                1.5     P < 0.01             Control  shWnt11         1.5     P < 0.01       1.5    P < 0.01
               mRNA levels  1.0        Wnt11                 45 kDa  protein expression  1.0  protein expression  1.0



               Relative Wnt11  0.5     CNN2                  13 kDa  Relative Wnt11  0.5   Relative CNN2  0.5





                  0                   GAPDH                  35 kDa    0                      0
                     Control  shWnt11                                     Control  shWnt11       Control  shWnt11
                                                                                            P < 0.01
                                                                                   100         P < 0.01
              C
                                                                                   (%)  80
                      Control              shWnt11            shWnt11+shCNN2                       P < 0.01
                      Control
                                                                                   Relative migration cells  60


                                                                                    40

                                                                                    20


                                                                                     0
                                                                                      Control  shWnt11
                                                                                      Control
                                                                                              shWnt11+shCNN2
                 A:qPCR was used to verify the transfection efficiency(n=6). B:Western blot was used to investigate changes in protein expression. C:Migration
              assay showing that liver cancer cells with simultaneous silencing of Wnt11 and CNN2(shWnt11+shCNN2)have a significantly reduced number of cells
              passing through the Transwell chamber compared to the Wnt11 interference group(shWnt11),Bar chart showing cell percentage(scale bar=100 μm,n=3).
                                    图5   Wnt/PCP信号通路影响CNN2表达促进肝癌细胞群体性迁移
                   Figure 5 The Wnt/PCP signaling pathway regulates CNN2 to influence collective migration of liver cancer cells

              移机制之间的精细交互,并探索靶向 ECM⁃细胞互                               大量研究表明,Wnt/PCP 信号通路在肿瘤的细
              作的精准干预策略,为抗转移治疗提供新的思路与                            胞群体性迁移中起重要作用,ECM与Wnt/PCP信号
              靶点。                                               通路协同调控肿瘤细胞的迁移                 [19- 20] 。CNN2 作为
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