biostudies-literatureRatze MAKNational Centre for the Replacement, Refinement and Reduction of Animals in ResearchMedical Research CouncilDutch Research Council (NWO)2932-2944https://www.ebi.ac.uk/biostudies/studies/S-EPMC9122823biostudies-literatureUnknown41(21)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. In the absence of anchorage, ILC cells undergo a sustained cell cycle arrest in G0/G1 while maintaining viability. From the genes that are upregulated in anchorage independent ILC cells, we selected Inhibitor of DNA binding 2 (Id2), a mediator of cell cycle progression. Using loss-of-function experiments, we demonstrate that Id2 is essential for anchorage independent survival (anoikis resistance) in vitro and lung colonization in mice. Importantly, we find that under anchorage independent conditions, E-cadherin loss promotes expression of Id2 in multiple moOncogeneLoss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer.PMC9122823NC/P001262/1016.096.318Sijnesael TBassey-Archibong BEnserink LO'Leary LBakker ERMRichard FDerksen PWBViciano IRoca-Cusachs PJaksani SIsacke CMVisser Dvan Diest PJDesmedt Cvan de Ven RRatze MAKTutt ADaniel JMKoorman TFitzpatrick AfalseLoss 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. In the absence of anchorage, ILC cells undergo a sustained cell cycle arrest in G0/G1 while maintaining viability. From the genes that are upregulated in anchorage independent ILC cells, we selected Inhibitor of DNA binding 2 (Id2), a mediator of cell cycle progression. Using loss-of-function experiments, we demonstrate that Id2 is essential for anchorage independent survival (anoikis resistance) in vitro and lung colonization in mice. Importantly, we find that under anchorage independent conditions, E-cadherin loss promotes expression of Id2 in multiple mo2022-01-01T00:00:00Z2022 May2025-04-04T07:34:19.781Z2025-02-19T01:24:00.292ZS-EPMC91228233543730810.1038/s41388-022-02314-w