Loss of Rnd3/RhoE induces entosis in human hepatocellular carcinoma

Entosis is a process that leads to the formation of cell-in-cell structures commonly found in cancers. Here, we identified entosis in hepatocellular carcinoma and the loss of Rnd3 as an efficient inducer of this mechanism. We characterized the different stages and the molecular regulators of entosis induced after silencing of Rnd3. We demonstrated that this process is dependent on RhoA/ROCK pathway, but independent on E-cadherin. The proteomic analysis of entotic cells allowed us to identify LAMP-1 as a protein implicated not only in the degradation final stage of entosis, but also in the full mechanism. By analyzing entosis in human hepatocellular carcinoma samples, we found a relationship between the presence of entotic cells and the metastatic potential of tumors. Altogether, these data suggest the involvement of entosis in liver tumor progression and highlight a new perspective for the entosis analysis in medicine research as a novel therapeutic target.