Entosis has been found to be a different mechanism for cancer cells to form cell-in-cell structures at tumor sites. The entosis process in cancer cells is mediated via E-cadherin and P-cadherin. Since cadherins usually create homolytic cell to cell junctions, it is believed that the process mainly occurs between homologous cells. After cell-cell adhesions are mediated, the engulfed cells promote their own uptake into the neighbor cell. Additionally, they promote the ingestion process through actin polymerization and myosin contraction. The invading cell (outer cell) actomyosin contraction is regulated by controllers or cell tension such as
RhoA, furthermore they accumulate actin and myosin at the
cell cortex which generates the mechanical tension that generates the cell-in-cell invasion mechanism. The entosis mechanism can potentially have substantial energetic implication in cancer cells compared to other mechanisms of cell death and engulfment. A crucial part of the process is the active involvement of invading cells, which does not happen in other forms of cell engulfment. This allows the mechanism to selectively target living cells, excluding dead cells or non-living material such as cell debris. After internalization, engulfed cells are killed by the host cell following the maturation of the entotic
vacuole that encapsulates the entotic cell. The maturation of the entotic vacuole involves modification by autophagy pathway proteins, followed by lysosome fusion and inner cell dead and degradation inside the host cell. In this mechanism, the autophagy pathway proteins play an important role by scavenging extracellular nutrients derived from the inner cell death. Internalized cells can also undergo alternative fates such as apoptosis or unharmed escape from host cell. In clinical cancer specimens, evidence of DNA fragmentation has been found suggesting that non-apoptotic cell death may be a common fate for entotic cells in human cancers. Entosis correlates with cancer worse prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma, and some breast ductal carcinoma. In breast cancer, entosis correlates with two classical prognostic factors of breast cancer (HER2 and Ki67). In the analysis of entosis of the clinical case - calculations of the frequency of entosis showed that the highest frequency of entosis is during the formation of metastasis and when the neoplastic process is very advanced, the frequency of entotic structures decreases, suggesting entosis is a regulated process that varies according to stage. == Videos ==