Tumour specific HORMAD1 expression perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors - PubMed
a day ago
- #genomic instability
- #mitotic arrest
- #HORMAD1
- HORMAD1 is normally expressed in germ-line cells but is aberrantly expressed in 60% of triple-negative breast cancers (TNBCs).
- Out-of-context HORMAD1 expression in mitotic cells leads to mitotic arrest perturbation and aneuploidy.
- HORMAD1 weakens the spindle assembly checkpoint (SAC) and affects kinetochore-microtubule error correction.
- The mitotic effects of HORMAD1 are independent of MAD2L1 but involve interaction with Aurora B and defective Aurora B/INCENP signaling.
- Aberrant HORMAD1 expression increases sensitivity to MPS1, Aurora B, or BUB1 inhibitors, suggesting potential therapeutic targets.
- The study highlights how meiotic gene expression in tumors can cause genomic instability and identifies potential treatment avenues.