TTK/hMPS1 is an attractive therapeutic target for triple-negative breast cancer.
作者： Virginie Maire , Celine Baldeyron , Marion Richardson , Bruno Tesson , Anne Vincent-Salomon
DOI: 10.1371/JOURNAL.PONE.0063712
关键词: Cancer research 、 Targeted therapy 、 Triple-negative breast cancer 、 Protein kinase A 、 Cell cycle checkpoint 、 Population 、 Triple Negative Breast Neoplasms 、 Cell 、 Reverse phase protein lysate microarray 、 Biology 、 Molecular biology
摘要: Triple-negative breast cancer (TNBC) represents a subgroup of cancers (BC) associated with the most aggressive clinical behavior. No targeted therapy is currently available for treatment patients TNBC. In order to discover potential therapeutic targets, we searched protein kinases that are overexpressed in human TNBC biopsies and whose silencing cell lines causes death. A cohort including BC obtained at Institut Curie as well normal tissues has been analyzed gene-expression level. The data revealed kinase monopolar spindle 1 (hMPS1), also known TTK involved mitotic checkpoint, specifically TNBC, compared other subgroups healthy tissues. We confirmed by immunohistochemistry reverse phase array expressed higher levels subgroups. then determined biological effects depletion RNA interference, through analyses tumorigenic capacity viability different lines. found RNAi-mediated various severely compromised their ability form colonies an anchorage-independent manner. Moreover, observed led increase H2AX phosphorylation, activation caspases 3/7, sub-G1 population accumulation high annexin V staining, decrease G1 increased aneuploidy. Altogether, these indicate cells induces apoptosis. These results point out may represent attractive target this poor prognosis cancer.
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