A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion

Cell (2007) 131:966-979.

        Mammary glands are hollow ducts surrounded by fully differentiated epithelial cells anchored on extracellular matrix. The development and maintenance of the hollow structure was accomplished by anoikis, an apoptotic cell death induced by detachment of cells from extracellular matrix. During breast cancer development, transformed cells exhibit anchorage-independent cell growth and fill the luminal space of mammary glands; therefore, anoikis serves as a barrier for tumor formation and metastasis by inhibiting the anchorage-independent cell growth. However, previous studies showed that inhibition of apoptosis in human mammary epithelial cells only delayed the formation of hollow ducts, indicating that nonapoptotic cell death may serve as an alternative process of tumor suppression. In the present study, the authors demonstrated a new type of nonapoptotic cell death, entosis, may act as an intrinsic barrier for tumor formation. First, they found that nontransformed human mammary epithelial cells were internalized by neighboring cells in suspension cell culture after forming cell-cell contact by cadherins. In addition, the internalization process is independent of apoptosis but depends on the Rho and ROCK1/2 activities of the internalized cells. The authors defined this unique feature as entosis, which the internalized cells were actively participated in the process rather than passively engulfed by phagocytic cells. Most common fate of the internalized cells is death resulted from the acidification of lysosome. Furthermore, the authors demonstrated that entosis were commonly observed features referred as cell-in-cell or cell cannibalism in human primary and metastatic tumor species and may represent as an intrinsic tumor suppression mechanism for cell detached from extracellular matrix.

References

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