BRD4 promotes tumor progression and NF-κB/CCL2-dependent tumor-associated macrophage recruitment in GIST.,Cell Death & Disease

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BRD4 promotes tumor progression and NF-κB/CCL2-dependent tumor-associated macrophage recruitment in GIST.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41419-019-2170-4
Jianfeng Mu ₁ , Pengfei Sun ₂ , Zhiming Ma ₃ , Pengda Sun ₃

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The most commonly occurring sarcoma of the soft tissue is gastrointestinal stromal tumor (GIST). Treatment and prevention of the disease necessitate an understanding of the molecular mechanisms involved. However, the role of BRD4 in the progression of GIST is still unclear. While it is known there are abundant infiltrating tumor-associated macrophages (TAMs) in the tumor microenvironment, the exact role of these cells has yet to be studied. This work showed an upregulation of BRD4 in GIST that was associated with GIST prognosis. Through gain and loss of function studies, it was found that BRD4 promotes GIST growth and angiogenesis in vitro and in vivo. Mechanistically, BRD4 enhances CCL2 expression by activating the NF-κB signaling pathway. Furthermore, this CCL2 upregulation causes recruitment of macrophages into the tumor leading to tumor growth. A likely mechanism for interactions in the GIST microenvironment has been outlined by this work to show the role and potential use of BRD4 as a treatment target in GIST.

中文翻译：

BRD4 促进 GIST 中的肿瘤进展和 NF-κB/CCL2 依赖性肿瘤相关巨噬细胞募集。

最常见的软组织肉瘤是胃肠道间质瘤（GIST）。疾病的治疗和预防需要了解所涉及的分子机制。然而，BRD4 在 GIST 进展中的作用仍不清楚。虽然已知肿瘤微环境中有大量浸润性肿瘤相关巨噬细胞 (TAM)，但这些细胞的确切作用仍有待研究。这项工作显示 GIST 中 BRD4 的上调与 GIST 预后相关。通过功能获得和损失研究，发现 BRD4 在体外和体内促进 GIST 生长和血管生成。从机制上讲，BRD4 通过激活 NF-κB 信号通路来增强 CCL2 的表达。此外，这种 CCL2 上调导致巨噬细胞募集到肿瘤中，导致肿瘤生长。

更新日期：2019-12-09

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