Disruption of the Hippo pathway promotes the proliferation of childhood acute lymphoblastic leukemia cells, inhibits apoptosis and chemosensitivity

被引:0
作者
Jiang, Hao [1 ]
Zhang, Rui-Bo [1 ]
Peng, Juan [2 ]
Ren, Lan [1 ]
Wang, Heng-Dong [1 ]
机构
[1] Hubei Univ Med, Taihe Hosp, Dept Pediat, Shiyan 442000, Hubei, Peoples R China
[2] Hubei Univ Med, Taihe Hosp, Dept Blood Transfus, Shiyan, Hubei, Peoples R China
关键词
Childhood acute lymphoblastic leukemia; Hippo pathway; chemosensitivity; proliferation; apoptosis; SIGNALING PATHWAY; CANCER; YAP; YAP/TAZ; METASTASIS;
D O I
10.1080/17474086.2024.2356255
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundDespite advancements in chemotherapy and stem cell transplantation, the recurrence and chemoresistance of childhood acute lymphoblastic leukemia (cALL) remain a significant challenge, thus indicating the need for novel therapeutic targets. Research design and methodsThe protein levels of YAP1, p-YAP1, TAZ, and Cyr61 of cALL patients and healthy volunteers were measured by western blot analysis. Then the leukemic cell line SUP-B15 was transfected with sh-YAP1 and pcDNA3.1-YAP1 to knockdown or overexpress YAP1. The viability, chemosensitivity, apoptosis, migration, and invasion of SUP-B15 cells were determined by MTT, flow cytometry, and Transwell assay. ResultsThe cALL patients had higher YAP1, TAZ, and Cyr61 protein expression and lower p-YAP1 protein expression in bone marrow tissues compared with healthy volunteers (p < 0.01). In SUP-B15 cells, YAP1 knockdown upregulated p-YAP1 protein expression (p < 0.01) and downregulated TAZ and Cyr61 protein expression (p < 0.01). In addition, knocking down YAP1 significantly inhibited cell viability, migration, and invasion, and induced apoptosis (p < 0.01). YAP1 knockdown also reduced the IC50 value following treatment with vincristine, daunorubicin, cyclophosphamide, and dexamethasone (p < 0.05). ConclusionsDisruption of the Hippo pathway attenuates the development of cALL by promoting cell proliferation while suppressing apoptosis and drug sensitivity.
引用
收藏
页码:269 / 274
页数:6
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