Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer

Invasive lobular breast carcinoma (ILC) is characterized by proliferative indolence and long-term latency relapses. This study aimed to identify how disseminating ILC cells control the balance between quiescence and cell cycle re-entry. The present study demonstrate that Id2 is essential for anchorage independent survival (anoikis resistance) in vitro and lung colonization in mice using loss-of-function experiments. The study finds that under anchorage independent conditions, E-cadherin loss promotes expression of Id2 in multiple mice and (organotypic) human models of ILC. Furthermore, this study indicates that loss of E-cadherin and subsequent expression of Id2 drive indolence and dissemination of ILC. E-cadherin and Id2 are promising candidates to stratify low and intermediate grade invasive breast cancers for the use of clinical cell cycle intervention drugs.