Although cell-in-cell structures (CICs) could be detected in a wide range of human
tumors, homotypic CICs formed between
tumor cells occur at low rate for most of them. We recently reported that
tumor cells lacking expression of E- and
P-cadherin were incapable of forming homotypic CICs by entosis, and re-expression of E- or
P-cadherin was sufficient to induce CICs formation in these
tumor cells. In this work, we found that homotypic CICs formation was impaired in some
tumor cells expressing high level of
E-cadherin due to loss expression of
alpha-catenin (α-
catenin), a molecular linker between
cadherin-mediated adherens junctions and
F-actin. Expression of α-
catenin in these
tumor cells restored cell-cell adhesion and promoted CICs formation in a ROCK
kinase-dependent way. Thus, our work identified α-
catenin as another molecule in addition to E- and
P-cadherin that were targeted to inactivate homotypic CICs formation in human
tumor cells.