首页|CLIP170通过TGF-β通路抑制甲状腺乳头状癌的转移

CLIP170通过TGF-β通路抑制甲状腺乳头状癌的转移

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目的:研究细胞质连接蛋白 170(cytoplasmic linker protein 170,CLIP170)是否影响甲状腺乳头状癌(papillary thyroid cancer,PTC)细胞的转移和侵袭并阐明其机制.方法:通过GEO和TCGA数据分析CLIP170在PTC中的表达水平;通过慢病毒转染技术构建CLIP170敲减细胞,Transwell转移和侵袭实验评估其功能;通过免疫荧光观察CLIP170对细胞肌动蛋白结构的影响;以ELISA方法检测细胞培养基中转化生长因子-β(transforming growth factor-β,TGF-β)1的释放;通过免疫印迹和实时定量荧光PCR方法检测上皮-间充质转化(epithelial-mesenchymal transition,EMT)和TGF-β信号通路分子的表达量并最终在裸鼠肺转移模型中验证.结果:CLIP170在PTC中的表达量比在正常甲状腺组织中的表达量低.功能方面,CLIP170KD在体外和体内均显著增强了PTC细胞的转移;机制方面,CLIP170KD触发了TGF-β通路的激活,促进肿瘤细胞的迁移和侵袭.TGF-β的抑制剂有效抑制了TGF-β活性,并显著逆转CLIP170KD所诱导的肿瘤转移.结论:CLIP170有望成为一种缓解有转移倾向的PTC的治疗靶点.
Cytoplasmic linker protein 170 inhibits papillary thyroid cancer cell metastasis through the TGF-β pathway
Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.

cytoplasmic linker protein 170(CLIP170)papillary thyroid cancer(PTC)metastasisepithelial-mesenchymal transition(EMT)TGF-β pathway

马斌媛、许亚鑫、潘云燕、巫娅妮、高宏伟

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兰州大学第二医院检验医学中心(兰州市 731000)

甘肃省人民医院检验医学中心

兰州大学第二临床医学院

CLIP170 甲状腺乳头状癌 转移 上皮间质转化 TGF-β通路

国家自然科学基金面上项目甘肃省科技计划自然科学研究项目甘肃省科技计划自然科学研究项目兰州大学大学生创新创业训练计划行动计划

8197249823JRRA163422JR11RA05520230050052

2024

10.12354/j.issn.1000-8179.2024.20240154

中国肿瘤临床
中国抗癌协会

中国肿瘤临床

CSTPCD北大核心
影响因子：1.32
ISSN：1000-8179
年,卷(期)：2024.51(5)
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