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

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

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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 YAP 1-Ser 127 phosphorylation levels.YAP 1-Ser 127 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.

acute lymphoblastic leukemialarge tumor suppressor kinase 1phosphorylationRNA-SeqYes1-associated protein

Feng ZHANG、Mohammed Awal Issah、Hai-ying FU、Hua-rong ZHOU、Ting-bo LIU、Jian-zhen SHEN

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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

Tamale Technical University,Faculty of Allied Health and Pharmaceutical Sciences,Department of Medical Laboratory Technology,Tamale NS-011-2000,Ghana

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

2024

10.1007/s11596-023-2821-7

当代医学科学(英文)
华中科技大学同济医学院

当代医学科学(英文)

影响因子：0.748
ISSN：2096-5230
年,卷(期)：2024.44(1)
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