Compounding the underlying complexities associated with tumorigenesis, the functional consequences of the establishment of heterotypic cadherin interactions between cancer cells and fibroblasts in promoting collective invasion are opening up a new way in which tumors exploit the tumor-promoting microenvironment to acquire malignant characteristics, in particular in metastatic tumors that do not undergo EMT events and still maintain the expression of E-cadherin at the membrane45,46. This evidence concerns the gene CDH1 and neoplasm.