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碳酸酐酶IX通过调节PFKFB4表达促进人宫颈癌细胞运动。

Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression.

作者信息

Hsin Min-Chieh, Hsieh Yi-Hsien, Hsiao Yi-Hsuan, Chen Pei-Ni, Wang Po-Hui, Yang Shun-Fa

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.

Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan.

出版信息

Cancers (Basel). 2021 Mar 9;13(5):1174. doi: 10.3390/cancers13051174.

DOI:10.3390/cancers13051174
PMID:33803236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7967120/
Abstract

Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIX/PFKFB4 expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.

摘要

碳酸酐酶IX（CAIX）是一种缺氧诱导蛋白，在多种人类癌症中高表达。然而，CAIX与人类宫颈癌转移所涉及的分子机制仍知之甚少。在本研究中，SiHa细胞中CAIX的过表达增加了细胞迁移和上皮-间质转化（EMT）。在Caski细胞系中沉默CAIX降低了细胞的运动性和EMT。此外，RNA测序分析确定了一个靶基因，双功能6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶（PFKFB4），它受CAIX过表达和敲低的影响。在TCGA数据库的宫颈癌中发现CAIX表达与PFKFB4水平呈正相关。机制上，CAIX过表达激活细胞外信号调节激酶（ERK）的磷酸化，以诱导EMT并促进细胞迁移。在临床结果中，CAIX/PFKFB4在晚期表达的人类宫颈癌患者有更高的淋巴结转移率和最短的生存时间。我们的研究发现，CAIX过表达增加PFKFB4表达和EMT，促进宫颈癌细胞迁移。CAIX可能促成宫颈癌细胞转移，抑制它可能是一种宫颈癌治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/b110d9ec75f0/cancers-13-01174-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/d167178a8b11/cancers-13-01174-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/8bb9b76debef/cancers-13-01174-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/3c1791bd0e6b/cancers-13-01174-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/5f421a7407f3/cancers-13-01174-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/b110d9ec75f0/cancers-13-01174-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/d167178a8b11/cancers-13-01174-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/8bb9b76debef/cancers-13-01174-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/3c1791bd0e6b/cancers-13-01174-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/5f421a7407f3/cancers-13-01174-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5254/7967120/b110d9ec75f0/cancers-13-01174-g005.jpg

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