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叉头框Q1对结直肠癌的血管生成和巨噬细胞募集至关重要。

Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer.

作者信息

Tang Hui, Zheng Ji, Bai Xuan, Yue Ke-Lin, Liang Jian-Hua, Li Dan-Yang, Wang Lin-Ping, Wang Jin-Li, Guo Qiang

机构信息

Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.

Medical Faculty, Kunming University of Science and Technology, Kunming, China.

出版信息

Front Oncol. 2020 Nov 30;10:564298. doi: 10.3389/fonc.2020.564298. eCollection 2020.

Abstract

Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.

摘要

血管生成和肿瘤微环境(TME)在肿瘤发生过程中发挥着重要作用。叉头框Q1(FOXQ1)是多种肿瘤(包括结直肠癌,CRC)中公认的致癌基因;然而,FOXQ1是否促进CRC中的血管生成和TME修饰在很大程度上仍不清楚。在这里,我们证明了FOXQ1诱导的血管生成和巨噬细胞募集在CRC中的重要作用,这与其通过激活EGF/PDGF途径和Twist1/CCL2轴促进内皮细胞和巨噬细胞迁移的能力有关。我们还提供证据表明,FOXQ1、Twist1、CCL2和巨噬细胞浸润之间的临床意义与CRC患者8年生存率降低相关。我们的研究结果表明,FOXQ1在CRC的恶性肿瘤和进展中起关键作用,因此,FOXQ1可能作为抑制CRC血管生成和减少巨噬细胞募集的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cfa/7734287/1e3427aed5dd/fonc-10-564298-g001.jpg

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