搜索条件
找到 1 条目
每页显示结果数
搜索结果
- Type:
- Collection
- 摘抄:
- Background: Non-muscle myosin IIA (NMIIA; encoded by MYH9) has been implicated in breast cancer progression; however, its clinical significance and therapeutic potential in HER2-positive (HER2+) breast cancer remain poorly defined. We investigated the clinical significance of NMIIA and evaluated the anti-tumour activity of the selective NMII inhibitor MT-228. Methods: NMIIA expression was evaluated by immunohistochemistry in a cohort of 1,142 patients with early-stage invasive breast cancer. Molecular docking and molecular dynamics simulations were performed to characterize binding of MT-228 to NMIIA. The effects of MT-228 were assessed in breast cancer cell lines using assays of cell viability, migration, three-dimensional invasion, DNA damage, apoptosis, and combination studies with FDA approved HER kinase inhibitors Neratinib and Tucatinib. Results: High NMIIA expression was associated with adverse clinical outcomes in patients with HER2 immunoreactive breast cancer. Computational analyses demonstrated that MT-228 forms favorable binding interactions and stabilized the NMIIA motor domain. MT-228 inhibited cell growth across multiple breast cancer subtypes. In HER2+ cell lines, MT-228 suppressed migration and 3D invasion, increased γH2AX foci formation, caspase-3/7 enzyme activity, and PARP cleavage, and enhanced the anti-proliferative activity of Neratinib and Tucatinib. Conclusions: Our findings identify NMII as a potential therapeutic target in HER2 immunoreactive breast cancer and support further investigation of selective NMII inhibition either alone or in combination with anti-HER therapies.
- 作者:
- Feroz, Wasim and Garrett, Joan
- 提交者:
- Joan Garrett
- 证书:
- Attribution 4.0 International