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脂肪酸结合蛋白4(FABP4)在癌症中的治疗意义:一个新兴的抗癌靶点

Therapeutic Implications of FABP4 in Cancer: An Emerging Target to Tackle Cancer.

作者信息

Sun Naihui, Zhao Xing

机构信息

Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Front Pharmacol. 2022 Jul 11;13:948610. doi: 10.3389/fphar.2022.948610. eCollection 2022.

Abstract

Metabolic reprogramming is an emerging hallmark of tumor cells. In order to survive in nutrient-deprived environment, tumor cells rewire their metabolic phenotype to provide sufficient energy and build biomass to sustain their transformed state and promote malignant behaviors. Fatty acid uptake and trafficking is an essential part of lipid metabolism within tumor cells. Fatty acid-binding proteins (FABPs), which belongs to a family of intracellular lipid-binding protein, can bind hydrophobic ligands to regulate lipid trafficking and metabolism. In particular, adipocyte fatty acid binding protein (FABP4), one of the most abundant members, has been found to be upregulated in many malignant solid tumors, and correlated with poor prognosis. In multiple tumor types, FABP4 is critical for tumor proliferation, metastasis and drug resistance. More importantly, FABP4 is a crucial driver of malignancy not only by activating the oncogenic signaling pathways, but also rewiring the metabolic phenotypes of tumor cells to satisfy their enhanced energy demand for tumor development. Thus, FABP4 serves as a tumor-promoting molecule in most cancer types, and may be a promising therapeutic target for cancer treatment.

摘要

代谢重编程是肿瘤细胞新出现的一个特征。为了在营养匮乏的环境中存活,肿瘤细胞会重塑其代谢表型,以提供足够的能量并构建生物量,以维持其转化状态并促进恶性行为。脂肪酸摄取和转运是肿瘤细胞内脂质代谢的重要组成部分。脂肪酸结合蛋白(FABPs)属于细胞内脂质结合蛋白家族,可结合疏水性配体以调节脂质转运和代谢。特别是,脂肪细胞脂肪酸结合蛋白(FABP4)是含量最丰富的成员之一,已发现在许多恶性实体瘤中上调,并与预后不良相关。在多种肿瘤类型中,FABP4对肿瘤增殖、转移和耐药性至关重要。更重要的是,FABP4不仅通过激活致癌信号通路,还通过重塑肿瘤细胞的代谢表型以满足其对肿瘤发展增强的能量需求,从而成为恶性肿瘤的关键驱动因素。因此,FABP4在大多数癌症类型中作为一种肿瘤促进分子,可能是癌症治疗中一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b33/9310032/f9ed6c9a3510/fphar-13-948610-g001.jpg

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