We used ~normal human mammary epithelial cells (HMECs) to test CDH1 loss (modeling ILC) vs inhibiting E-cadherin, i.e. genetic suppression vs signaling block, to define how CDH1 loss is fundamentally different that 'simply' losing E-cadh mediated cell contacts. I.e. is this ~EMT, or not? 2/n

As we learn more re CDH1 loss-induced lineage reprogramming, we can develop new risk assessment strategies for benign ILC precursors, build prevention strategies, and target "truncal" effects of CDH1 loss in overt ILC to target the changes that likely are important in every single cancer cell. 5/5

So CDH1 loss causes a lineage remodeling in normal HMEC, locking cells in a new luminal progenitor-like state. This may explain why nearly all ILC are luminal-type (i.e. ER+) and point to CDH1 loss as a critical "bottleneck" in breast oncogenesis specific to ILC. 4/n