CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways.
CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways.
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CRLF1通过激活MAPK/ERK和PI3K/AKT通路促进甲状腺乳头状癌的恶性表型
DOI：
10.1038/s41419-018-0352-0
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发表时间：
2018-03-07
影响因子：
9
通讯作者：
Huang XM
中科院分区：
文献类型：
--
作者：
Yu ST;Zhong Q;Chen RH;Han P;Li SB;Zhang H;Yuan L;Xia TL;Zeng MS;Huang XM
甲状腺乳头状癌（PTC）是最常见的内分泌癌之一，预后不一。来自预后不良患者的肿瘤可能差异表达特定基因。因此，对癌症基因组图谱（TCGA）数据库进行分析，发现细胞因子受体样因子1（CRLF 1）可能是PTC治疗的潜在新靶点。本研究旨在探讨CRLF 1在PTC中的表达及其在PTC发病中的作用和机制。甲状腺乳头状癌组织CRLF 1在mRNA和蛋白水平的表达均高于正常甲状腺组织。高CRLF 1水平与侵袭性临床病理特征和低无病生存率相关。通过使用功能丧失和功能获得测定，我们发现CRLF 1不仅在体外增加细胞迁移和侵袭，而且在体外和体内促进肿瘤生长。此外，CRLF 1诱导上皮-间充质转化。CRLF 1的过表达激活了ERK 1/2和AKT通路。通过用MEK抑制剂U 0126或AKT抑制剂MK-2206处理细胞来抑制CRLF 1诱导的致癌作用。这些结果表明，CRLF 1增强PTC中的细胞增殖和转移，因此可能是PTC的潜在治疗靶点。
Papillary thyroid carcinoma (PTC) is the one of the most common types of endocrine cancer and has a heterogeneous prognosis. Tumors from patients with poor prognosis may differentially express specific genes. Therefore, an analysis of The Cancer Genome Atlas (TCGA) database was performed and revealed that cytokine receptor-like factor 1 (CRLF1) may be a potential novel target for PTC treatment. The objective of the current study was to explore the expression of CRLF1 in PTC and to investigate the main functions and mechanisms of CRLF1 in PTC. PTC tissues exhibited higher CRLF1 expression at both the mRNA and protein levels than it did with normal thyroid tissues. High CRLF1 levels were associated with aggressive clinicopathological features and poor disease-free survival rates. By using loss-of-function and gain-of-function assays, we found that CRLF1 not only increased cell migration and invasion in vitro but also promoted tumor growth both in vitro and in vivo. In addition, CRLF1 induced epithelial–mesenchymal transitions. Overexpression of CRLF1 activated the ERK1/2 and AKT pathways. The oncogenic effects induced by CRLF1 were suppressed by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor MK-2206. These results suggest that CRLF1 enhances cell proliferation and metastasis in PTC and thus may therefore be a potential therapeutic target for PTC.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
9
作者：
通讯作者：
--
影响因子：
3.4
作者：
Gonzalez Fernandez, D.;Lazaro Perez, M.;Perez Oliva, N.
通讯作者：
Perez Oliva, N.
影响因子：
4.8
作者：
Lelièvre, E;Plun-Favreau, H;Gascan, H
通讯作者：
Gascan, H
影响因子：
6.6
作者：
Cazarin, Juliana M.;Coelho, Raquel G.;Carvalho, Denise P.
通讯作者：
Carvalho, Denise P.