GAS2增强CXCR4蛋白稳定性并促进T-ALL细胞的生长  

Growth Arrest-specific 2 Enhances CXCR4 Stability and Promote the Growth of T Cell Acute Lymphoblastic Leukemia Cells

作　　者：田自丰 张建祥 赵昀 马文娟 TIAN Zi-feng;ZHANG Jian-xiang;ZHAO Yun;MA Wen-juan(School of Radiation Medicine and Protection,Suzhou Medical College,Soochow University,Suzhou,Jiangsu,215123,China;Cyrus Tang Hematology Center,Soochow University,Suzhou,Jiangsu,215123,China)

机构地区：[1]苏州大学苏州医学院放射医学与防护学院,江苏苏州215123 [2]苏州大学唐仲英血液学研究中心,江苏苏州215123

出　　处：《中国血液流变学杂志》2024年第2期182-189,共8页Chinese Journal of Hemorheology

基　　金：国家自然科学基金青年项目(81800151)。

摘　　要：目的研究生长抑制特异蛋白GAS2(growth arrest-specific 2)在急性T淋巴细胞白血病(T-cell acute lymphoblastic leukemia,T-ALL)细胞体内外生长和迁移中的功能,并初探其作用机制。方法(1)以MOLT-4细胞为模型,研究过表达GAS2对这些细胞的生长、集落生成、迁移和体内成白血病能力的影响;(2)利用RT-qPCR、Western blot和流式细胞术研究GAS2对CXCR4表达的影响;(3)在过表达GAS2的MOLT-4细胞中沉默CXCR4,研究CXCR4在GAS2促进T-ALL细胞生长功能中的作用。结果(1)过表达GAS2显著增强MOLT-4细胞的生长、集落生成和迁移能力;(2)过表达GAS2增强MOLT-4细胞在免疫缺陷小鼠体内的成白血病的能力;(3)GAS2增强CXCR4的蛋白表达、细胞膜表达和稳定性,但不影响它的mRNA表达;(4)CXCR4沉默能逆转过表达GAS2所导致的MOLT-4细胞生长增快。结论GAS2可部分通过增强CXCR4的蛋白稳定性而促进T-ALL细胞的生长。该研究增进了对T-ALL分子致病机制的认知,有望为疾病治疗提供新思路。Objective To study the effects of growth arrest-specific 2(GAS2)on the proliferation in vitro and vivo and migration of acute T cell lymphoblastic leukemia(T-ALL)cells and to delineate the underlying mechanisms.Methods(1)Using MOLT-4 cells as model,the effects of GAS2 overexpression on the proliferation,colony forming-cell production,migration and leukemogenesis of these cells were studied.(2)RT-qPCR,Western blot and flow cytometry were utilized to analyze the effects of GAS2 overexpression on CXCR4 expression.(3)CXCR4 was silenced in GAS2 overexpression MOLT-4 cells and then to study the role of CXCR4 in promoting the growth of T-ALL cells.Results(1)GAS2 overexpression significantly promoted the proliferation,colony forming-cell production and migration of MOLT-4 cells.(2)GAS2 overexpression significantly promoted the leukemogenesis ability of MOLT-4 cells.(3)GAS2 overexpression enhanced the protein expression of CXCR4,the membrane expression of CXCR4 and the protein stability of CXCR4.(4)Silence of CXCR4 diminished the proliferation enhancement induced by GAS2 overexpression.Conclusion GAS2 promotes the growth of T-ALL cells partially through its enhancement of the protein stability of CXCR4,which deepens the understanding of T-ALL pathology and possibly provides new clue to improve the disease treatment.

关 键 词：急性T淋巴细胞白血病 GAS2 CXCR4 

分 类 号：R733.71[医药卫生—肿瘤]