HORMAD1 drives spindle assembly checkpoint defects and sensitivity to multiple mitotic kinases

Background: The study aimed to identify and target effects associated with HORMAD1 expression in breast cancer cells. Materials methods: Isogenic cell line models inducible were used dependencies induced by expression. Results: Expression of HORMAD1, a gene whose function is best understood meiosis, usually restricted germ-line cells but becomes aberrantly expressed 60% triple-negative cancers (TNBCs), where clearly bimodal distribution signatures genomic instability. Here, we report that mitotic leads defects the spindle assembly checkpoint (SAC). These observed despite functional MAD2-dependent SAC activity, instead consequence an interaction disruption chromosome passenger complex, leading decreased Aurora B signalling. HORMAD1-driven also excessive instability cellular sensitivity MPS1, BUB1 inhibitors, all which are great clinical interest TNBC. Conclusions: Our data demonstrate aberrant defects, highlights several therapeutic targets for large subset express HORMAD1. This may be relevant wider group high need similarly HORMAD1expression. Conflict interest: Ownership: CJL has stock in: Tango, Ovibio, Enedra Tx., Hysplex ANJT InBiomotion Advisory Board: CJL: Syncona, Sun Pharma, Gerson Lehrman Group, Merck KGaA, Vertex, AstraZeneca, 3rd Rock, Ono Artios, Abingworth, Tesselate. ANJT: Pfizer, Prime Oncology, Inbiomotion, Gilead, Corporate-sponsored Research: Artios Medivation Oncology