LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis.
LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis.
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DOI：
10.1038/s41416-022-01902-7
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发表时间：
2022-10
影响因子：
8.8
通讯作者：
Yuan, Yawei
中科院分区：
文献类型：
--
作者：
Xie, Tao;Du, Kunpeng;Liu, Wei;Liu, Chunshan;Wang, Baiyao;Tian, Yunhong;Li, Rong;Huang, Xiaoting;Lin, Jie;Jian, Haifeng;Zhang, Jian;Yuan, Yawei
远处转移和复发仍然是鼻咽癌（NPC）治疗的主要障碍。然而，人们对鼻咽癌生长和转移的分子机制知之甚少。使用定量逆转录聚合酶链反应、蛋白质印迹和免疫组织化学测定检测鼻咽癌细胞系和鼻咽癌组织中的 LHX2 表达。使用过表达或沉默LHX2的NPC细胞进行CCK-8测定、集落形成测定、EdU测定、体外伤口愈合和侵袭测定。异种移植肿瘤模型和肺转移模型参与体内测定。应用基因集富集分析（GSEA）、ELISA测定、蛋白质印迹、染色质免疫沉淀（ChIP）测定和荧光素酶报告基因测定来研究下游靶点机制。 LIM-同源域转录因子 2 (LHX2) 在鼻咽癌组织和细胞系中上调。 LHX2 升高与 NPC 患者的生存率较差密切相关。异位LHX2过表达在体外和体内均显着促进NPC细胞的生长、迁移和侵袭。从机制上讲，LHX2转录增加成纤维细胞生长因子1（FGF1）的表达，进而以自分泌和旁分泌的方式激活STAT3（信号转导和转录激活子3）、ERK1/2（细胞外调节蛋白激酶1/2）和AKT信号通路的磷酸化，从而促进鼻咽癌的生长和转移。用siRNA或FGFR抑制剂抑制FGF1可阻断LHX2诱导的鼻咽癌细胞生长、迁移和侵袭。我们的研究发现 LHX2-FGF1-FGFR 轴在 NPC 进展中发挥关键作用，并为 NPC 治疗提供了潜在靶点。
Distant metastasis and recurrence remain the main obstacle to nasopharyngeal carcinoma (NPC) treatment. However, the molecular mechanisms underlying NPC growth and metastasis are poorly understood. LHX2 expression was examined in NPC cell lines and NPC tissues using quantitative reverse transcription-polymerase chain reaction, western blotting and Immunohistochemistry assay. NPC cells overexpressing or silencing LHX2 were used to perform CCK-8 assay, colony-formation assay, EdU assay, wound-healing and invasion assays in vitro. Xenograft tumour models and lung metastasis models were involved for the in vivo assays. The Gene Set Enrichment Analysis (GSEA), ELISA assay, western blot, chromatin immunoprecipitation (ChIP) assay and Luciferase reporter assay were applied for the downstream target mechanism investigation. LIM-homeodomain transcription factor 2 (LHX2) was upregulated in NPC tissues and cell lines. Elevated LHX2 was closely associated with poor survival in NPC patients. Ectopic LHX2 overexpression dramatically promoted the growth, migration and invasion of NPC cells both in vitro and in vivo. Mechanistically, LHX2 transcriptionally increased the fibroblast growth factor 1 (FGF1) expression, which in turn activated the phosphorylation of STAT3 (signal transducer and activator of transcription 3), ERK1/2 (extracellular regulated protein kinases 1/2) and AKT signalling pathways in an autocrine and paracrine manner, thereby promoting the growth and metastasis of NPC. Inhibition of FGF1 with siRNA or FGFR inhibitor blocked LHX2-induced nasopharyngeal carcinoma cell growth, migration and invasion. Our study identifies the LHX2-FGF1-FGFR axis plays a key role in NPC progression and provides a potential target for NPC therapy.
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影响因子：
4.8
作者：
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通讯作者：
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11.2
作者：
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通讯作者：
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DOI：
10.1186/s13046-019-1023-4
发表时间：
2019-02-21
影响因子：
11.3
作者：
Liang, Tian-Song;Zheng, Ying-Juan;Liu, Zhang-Suo
通讯作者：
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