HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells - PubMed
5 hours ago
- #breast cancer
- #HES1
- #cell cycle
- HES1 oscillations are crucial for cell cycle reentry in estrogen receptor-positive (ER+) breast cancer cells.
- Long-term recurrence in breast cancer is driven by reactivation of dormant disseminated tumor cells (DTCs), especially in ER+ tumors.
- HES1, a Notch pathway transcription factor, regulates key cell cycle genes and exhibits protein expression oscillations.
- A model was developed using CDK4/6 inhibition (CDK4/6i) with palbociclib to study HES1 oscillations during cell cycle arrest and reentry.
- HES1 oscillations (~24 h) were lost during CDK4/6i-mediated arrest, with HES1 levels moderately higher and exhibiting smaller dips.
- Preventing the HES1 dip at cell cycle reentry upregulated p21, impeded reentry, and induced cell death.
- Manipulating HES1 dynamics could be a therapeutic approach to prevent reactivation of dormant tumor cells.