文章：

LOX-1和癌症：不可分割的联系

LOX-1 and cancer: an indissoluble liaison

原文发布日期：2021-01-05 

英文摘要：

Recently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on metabolic targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for the recognition, binding, and internalization of ox-LDL. In the past, several studied, aimed to clarify the role of LOX-1 receptor in atherosclerosis, shed light on its role in the stimulation of the expression of adhesion molecules, pro-inflammatory signaling pathways, and pro-angiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. In recent years, LOX-1 upregulation in different tumors evidenced its involvement in cancer onset, progression and metastasis. In this review, we outline the role of LOX-1 in tumor spreading and metastasis, evidencing its function in VEGF induction, HIF-1alpha activation, and MMP-9/MMP-2 expression, pushing up the neoangiogenic and the epithelial–mesenchymal transition process in glioblastoma, osteosarcoma prostate, colon, breast, lung, and pancreatic tumors. Moreover, our studies contributed to evidence its role in interacting with WNT/APC/β-catenin axis, highlighting new pathways in sporadic colon cancer onset. The application of volatilome analysis in high expressing LOX-1 tumor-bearing mice correlates with the tumor evolution, suggesting a closed link between LOX-1 upregulation and metabolic changes in individual volatile compounds and thus providing a viable method for a simple, non-invasive alternative monitoring of tumor progression. These findings underline the role of LOX-1 as regulator of tumor progression, migration, invasion, metastasis formation, and tumor-related neo-angiogenesis, proposing this receptor as a promising therapeutic target and thus enhancing current antineoplastic strategies. 

摘要翻译： 

近期研究表明，代谢紊乱与肿瘤发生发展之间存在显著相关性，这为针对代谢靶点制定新型治疗策略指明了方向。OLR1基因编码的LOX-1受体蛋白负责氧化低密度脂蛋白（ox-LDL）的识别、结合与内化。早期多项针对LOX-1受体在动脉粥样硬化中作用的研究揭示：该受体在血管内皮细胞和巨噬细胞中能刺激黏附分子表达、激活促炎信号通路并诱导促血管生成蛋白（如NF-kB和VEGF）的产生。近年来，LOX-1在多种肿瘤中的上调现象证实其参与癌症的发生、进展及转移过程。本文综述了LOX-1在肿瘤扩散和转移中的作用，通过证实其在VEGF诱导、HIF-1α激活及MMP-9/MMP-2表达中的功能，阐明该受体能促进胶质母细胞瘤、骨肉瘤、前列腺癌、结肠癌、乳腺癌、肺癌及胰腺肿瘤的新生血管生成和上皮-间质转化进程。此外，我们的研究还发现其通过与WNT/APC/β-连环蛋白通路相互作用，在散发性结肠癌发生中构建新的致病途径。对高表达LOX-1荷瘤小鼠进行的挥发性组学分析显示，其与肿瘤演进存在相关性，表明LOX-1上调与个体挥发性化合物的代谢变化密切关联，这为肿瘤进展提供了一种简便无创的替代监测方案。这些发现强调了LOX-1作为肿瘤进展、迁移、侵袭、转移形成及肿瘤相关新生血管生成调控因子的作用，表明该受体是具有潜力的治疗靶点，有望增强现有抗肿瘤策略的有效性。

原文链接：

LOX-1 and cancer: an indissoluble liaison