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FGFRL1 通过与 Hedgehog 信号通路的串扰促进卵巢癌进展。

FGFRL1 Promotes Ovarian Cancer Progression by Crosstalk with Hedgehog Signaling.

机构信息

Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.

Department of Pathology, The First Hospital of Huai'an City, Nanjing Medical University, Huai'an, 223001 Jiangsu, China.

出版信息

J Immunol Res. 2018 Feb 20;2018:7438608. doi: 10.1155/2018/7438608. eCollection 2018.

DOI:10.1155/2018/7438608
PMID:29675438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5838460/
Abstract

Fibroblast growth factor receptor-like-1 (FGFRL1) has been identified as the fifth fibroblast growth factor receptor. So far, little is known about its biological functions, particularly in cancer development. Here, for the first time, we demonstrated the roles of FGFRL1 in ovarian carcinoma (OC). An array and existing databases were used to investigate the expression profile of FGFRL1 and the relationship between FGFRL1 expression and clinicopathological parameters. FGFRL1 was significantly upregulated in OC patients, and high FGFRL1 expression was correlated with poor prognosis. cell proliferation, apoptosis and migration assays, and subcutaneous xenograft tumor models were used to determine the role of FGFRL1. Loss of function of FGFRL1 significantly influenced cell proliferation, apoptosis, and migration of OC cells and tumor growth . Chromatin immunoprecipitation PCR analysis and microarray hybridization were performed to uncover the mechanism. FGFRL1 expression could be induced by hypoxia through hypoxia-inducible factor 1, which directly binds to the promoter elements of FGFRL1. FGFRL1 promoted tumor progression by crosstalk with Hedgehog (Hh) signaling. Taken together, FGFRL1 is a potential predictor and plays an important role in tumor growth and Hh signaling which could serve as potential therapeutic targets for the treatment of OC.

摘要

成纤维细胞生长因子受体样 1(FGFRL1)已被鉴定为第五种成纤维细胞生长因子受体。迄今为止,人们对其生物学功能知之甚少,特别是在癌症发展方面。在这里,我们首次证明了 FGFRL1 在卵巢癌(OC)中的作用。使用阵列和现有数据库来研究 FGFRL1 的表达谱以及 FGFRL1 表达与临床病理参数之间的关系。FGFRL1 在 OC 患者中显著上调,并且高 FGFRL1 表达与预后不良相关。进行了细胞增殖、凋亡和迁移测定以及皮下异种移植肿瘤模型,以确定 FGFRL1 的作用。FGFRL1 的功能丧失显着影响 OC 细胞的增殖、凋亡和迁移,以及肿瘤生长。进行了染色质免疫沉淀 PCR 分析和微阵列杂交,以揭示其机制。FGFRL1 的表达可以通过缺氧诱导因子 1 通过缺氧诱导,该因子直接与 FGFRL1 的启动子元件结合而诱导。FGFRL1 通过与 Hedgehog(Hh)信号的串扰促进肿瘤进展。总之,FGFRL1 是一种潜在的预测因子,在肿瘤生长和 Hh 信号中起重要作用,可作为治疗 OC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/b6c1c873abf1/JIR2018-7438608.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/cf56bbe2f712/JIR2018-7438608.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/065de9ba50de/JIR2018-7438608.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/e30c857424dd/JIR2018-7438608.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/f6cdc4b665de/JIR2018-7438608.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/b6c1c873abf1/JIR2018-7438608.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/cf56bbe2f712/JIR2018-7438608.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/065de9ba50de/JIR2018-7438608.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/e30c857424dd/JIR2018-7438608.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/f6cdc4b665de/JIR2018-7438608.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/5838460/b6c1c873abf1/JIR2018-7438608.005.jpg

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