LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

查看全文 作　　者：Feng [1]ZHANG;Mohammed Awal [2]Issah;Hai-ying [3]FU;Hua-rong [1]ZHOU;Ting-bo [1]LIU;Jian-zhen [1]SHEN

机构地区：[1]Fujian Provincial Key Laboratory on Hematology,Fujian Medical Center of Hematology,Fujian Institute of Hematology,Clinical Research Center for Hematological Malignancies of Fujian Province,Fujian Medical University Union Hospital,Fuzhou 350001,China;[2]Tamale Technical University,Faculty of Allied Health and Pharmaceutical Sciences,Department of Medical Laboratory Technology,Tamale NS-011-2000,Ghana;[3]Department of Hematology,The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine,The Third People's Hospital of Fujian Province,Fuzhou 350122,China

出　　处：《Current Medical Science》索引2024年第44卷第1期,共12页

摘　　要：Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients. 关键词：acute lymphoblastic leukemia large tumor suppressor kinase 1 PHOSPHORYLATION RNA-Seq Yesl-associated protein

相关文献

参考文献（43）
引证文献（1）
耦合文献（60）

参考文献(43)

引证文献(1)

耦合文献(60)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

参考文献(43)

引证文献(1)

耦合文献(60)

用户提示