Tumor-intrinsic FABP5 is a novel driver for colon cancer cell growth via the HIF-1 signaling pathway
Tumor-intrinsic FABP5 is a novel driver for colon cancer cell growth via the HIF-1 signaling pathway
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DOI：
10.1016/j.cancergen.2021.11.001
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发表时间：
2021-11-11
期刊：
影响因子：
1.9
通讯作者：
Chun, Yang-Sook
中科院分区：
文献类型：
--
作者：
Seo, Jieun;Yun, JeongEun;Chun, Yang-Sook
脂质代谢功能失调是癌症发生和进展的已知原因，但对促进癌症进展的潜在分子机制知之甚少。在这项研究中，我们证明脂肪酸结合蛋白5 （FABP5）在结肠癌组织中升高，这种升高的表达与缺氧诱导因子-1 （HIF-1）信号通路的上调有关。在基于聚二甲基硅氧烷（PDMS）的三维（3D）培养芯片的生理体内模拟条件下，fabp5敲低的结肠癌细胞在整个培养期间表现出细胞生长减弱的现象。发现FABP5在缺氧条件下调节HIF-1 α信号通路内的HIF-lot蛋白水平和基因表达水平。我们的结果提供了支持使用FABP5作为结肠癌预后因素的证据。FABP5/HIF-1 α轴是改善脂肪酸引发的癌症进展的一个有希望的靶点。(C) 2021作者。Elsevier Inc.出版。
Dysfunctional lipid metabolism is a known cause of cancer development and progression, yet little is known about the underlying molecular mechanisms that contribute to cancer progression. In this study, we demonstrate that fatty acid binding protein 5 (FABP5) is elevated in colon cancer tissue and this increased expression is linked to upregulation of the hypoxia-inducible factor-1 (HIF-1) signaling pathway. Under physiologically in vivo mimicked conditions via a polydimethylsiloxane (PDMS)-based three-dimensional (3D) culture chip, FABP5-knockdown colon cancer cells exhibited attenuated cell growth throughout the culture period. FABP5 was found to regulate HIF-lot protein levels and gene expression levels within the HIF-1 alpha signaling pathway under hypoxic conditions. Our results provide evidence that supports the use of FABP5 as a prognostic factor in colon cancer. The FABP5/HIF-1 alpha axis is a promising target for ameliorating fatty acid-triggered cancer progression. (C) 2021 The Author(s). Published by Elsevier Inc.