Ras-ERK1/2-YAP axis mediates posterior cell proliferation in cancer cell clusters

Cell clusters are a prevalent form of cells in the body, and recent studies have found that they play a significant role in the malignant progression of tumors. Cell clusters can become malignant through cell–cell connectivity and the cell-interstitial microenvironment. However, the differences between anterior and posterior cells are still unclear. In this study, we identified that the proliferation rate of cells in the posterior cell zone was significantly higher than that in the anterior cell zone. This difference was positively related to the activation of Ras-ERK1/2-YAP axis. The leader cells in the anterior cell region had low expression of Ras-ERK1/2-YAP, which may be why they had inactive proliferation. This study also confirmed the importance of cytoskeleton in the process of cell proliferation. Loss of myosin inhibited both cell proliferation and the nuclear entry activation of ERK1/2-YAP. These findings are significant for understanding the proliferation of tumor cell clusters and identifying screening targets for anticancer drugs that weaken the mobility of tumor cells.