AXL对乳头状甲状腺癌STAT3信号通路活化的促进作用

AXL enhances STAT3 activation in papillary thyroid cancer

目的探讨AXL对乳头状甲状腺癌(papillary thyroid cancer,PTC) STAT3表达的影响。方法采用基因集富集分析的方法(gene set enrichment analysis,GSEA)对PTC转录组数据库中的572个PTC样本AXL的表达进行比较研究,分析AXL对PTC STAT3表达的影响。HEK293T细胞随机分为空白对照组、空载体组和pc DNA-AXL组(AXL组),Western blot检测各组p-STAT3的表达;用不同浓度的AXL配体GAS6处理BCPAP细胞系,Western blot检测细胞p-STAT3和核内STAT3的表达。结果 GSEA分析发现AXL高表达的PTC其STAT3信号通路活化程度更高(normalized enrichment score,NES)=1. 47,P <0. 05)。HEK293T细胞转染AXL后,AXL高表达导致p-STAT3活性增高(P <0. 05)。AXL配体GAS6处理BCPAP细胞系后,p-STAT3活性显著增高(P <0. 05),STAT3核转位增加(P <0. 01)。结论 AXL可促进PTCSTAT3信号通路的活化。

Objective Signal transducer and activator of transcription (STAT3)signaling is hyperactivated in papillary thyroid cancer(PTC),but the mechanism of which is not fully understood.AXL is upregualted in PTC which activates several signaling pathways.The objective of this article is to investigate whether AXL activates STAT3 signaling pathway. Methods The AXL of 572 PTC samples of the transcriptomes of PTC was analyzed by gene set enrichment analysis(GSEA)to assess the effect of AXL on activation of STAT3 signaling pathway.HEK293T cells were transfected by AXL plasmid and p-STAT3 level was determined by Western blot.PTC cell line BCPAP was treated with GAS6,and p-STAT3 and nuclear STAT3 were determined by Western blot. Results GSEA analysis found STAT3 activation was higher in AXL-high PTCs(Normalized enrichment score (NES)=1.47, P <0.05).HEK293T cells transfected with AXL displayed higher level of p-STAT3 ( P <0.05).Furthermore,treatment of PTC cell line BCPAP with GAS6,the ligand of AXL,led to increased p-STAT3 ( P <0.05) and more STAT3 nuclear translocation( P <0.05). Conclusion AXL increased STAT3 activation in PTC.