Anesthetic Propofol Promotes Tumor Metastasis in Lungs via GABA(A) R-Dependent TRIM21 Modulation of Src Expression.
Anesthetic Propofol Promotes Tumor Metastasis in Lungs via GABA(A) R-Dependent TRIM21 Modulation of Src Expression.
复制标题
麻醉药异丙酚通过 GABA(A)R 依赖性 TRIM21 调节 Src 表达促进肺肿瘤转移
DOI：
10.1002/advs.202102079
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Xie Z
中科院分区：
文献类型：
--
作者：
Liu Q;Sheng Z;Cheng C;Zheng H;Lanuti M;Liu R;Wang P;Shen Y;Xie Z
循环肿瘤细胞(CTCs)的产生是肿瘤转移的关键步骤，发生在手术切除肿瘤的过程中，通常在全身麻醉下进行。异丙酚是常用的麻醉剂，但其对CTCs和肿瘤转移的影响在很大程度上仍不清楚。在一个实验性的转移模型中，通过尾静脉注射低剂量或标准剂量的异丙酚到裸鼠体内，研究异丙酚的作用。丙泊酚或赋形剂治疗的肿瘤细胞也被注射到小鼠体内。采用体外肿瘤细胞-血管内皮细胞黏附试验、免疫荧光和其他方法评估异丙酚对肿瘤细胞黏附和伸展的影响。异丙酚诱导的小鼠肺肿瘤转移比对照组多。从机制上讲，异丙酚通过GABAAR增强肿瘤细胞的黏附和伸展，下调TRIM21的表达，导致与细胞黏附相关的蛋白质Src的上调。提示异丙酚可能通过GABAAR-TRIM21-Src机制促进肿瘤转移。常用麻醉剂异丙酚通过激活GABA受体，下调肿瘤转移调节蛋白TRIM21的表达，上调调节细胞黏附和伸展的蛋白Src的表达，从而促进小鼠肺部肿瘤的转移。这些数据表明，GABA受体-TRIM21-Src-肿瘤细胞的黏附/延伸是肿瘤转移的潜在机制。
Generation of circulating tumor cells (CTCs), a key step in tumor metastasis, occurs during surgical tumor resection, often performed under general anesthesia. Propofol is the commonly used anesthetic, but its effects on CTCs and tumor metastasis remain largely unknown. Propofol effects are investigated in an experimental metastasis model by injecting tumor cells and, subsequently, low‐ or standard‐dose propofol to nude mice through tail vein. Propofol‐ or vehicle‐treated tumor cells are also injected to the mice. An in vitro tumor cell–vascular endothelial cell adhesion assay, immunofluorescence, and other methods are employed to assess how propofol affects tumor cell adhesion and extension. Propofol induces more lung tumor metastasis in mice than control. Mechanistically, propofol enhances tumor cell adhesion and extension through GABAAR to downregulate TRIM21 expression, leading to upregulation of Src, a protein associated with cell adhesion. These results demonstrate that propofol may promote tumor metastasis through GABAAR–TRIM21–Src mechanism. The commonly used anesthetic propofol activates GABA receptors to downregulate expression of TRIM21, a protein mediating tumor metastasis, and consequently to upregulate expression of Src, a protein regulating cell adhesion and extension, leading to the promotion of tumor metastasis in lungs of mice. These data suggest GABA receptor–TRIM21–Src–tumor cell adhesion/extension as the underlying mechanism of tumor metastasis.
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影响因子：
5.3
作者：
Bai, DL;Pennefather, PS;Orser, BA
通讯作者：
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影响因子：
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作者：
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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