Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
Cardiology Unit, Department of Emergency and Critical Care, Tor Vergata Hospital, Rome, Italy.
Cancer Gene Ther. 2021 Nov;28(10-11):1088-1098. doi: 10.1038/s41417-020-00279-0. Epub 2021 Jan 5.
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.
最近，代谢紊乱、肿瘤发生和进展之间存在很强的相关性，这促使人们针对代谢靶点制定新的治疗策略。OLR1 基因编码 LOX-1 受体蛋白，负责识别、结合和内化 ox-LDL。过去的研究旨在阐明 LOX-1 受体在动脉粥样硬化中的作用，揭示其在血管内皮细胞和巨噬细胞中刺激黏附分子、促炎信号通路和促血管生成蛋白（包括 NF-kB 和 VEGF）表达中的作用。近年来，LOX-1 在不同肿瘤中的上调表明其参与了肿瘤的发生、进展和转移。在这篇综述中，我们概述了 LOX-1 在肿瘤扩散和转移中的作用，证明了其在诱导 VEGF、激活 HIF-1alpha 和表达 MMP-9/MMP-2 中的作用，促进了胶质母细胞瘤、骨肉瘤、前列腺癌、结肠癌、乳腺癌、肺癌和胰腺癌中的新生血管形成和上皮-间充质转化过程。此外，我们的研究还证明了其在与 WNT/APC/β-catenin 轴相互作用中的作用，突出了散发性结肠癌发生的新途径。在高表达 LOX-1 的荷瘤小鼠中进行挥发物分析的应用与肿瘤的演变相关，表明 LOX-1 的上调与个体挥发性化合物代谢变化之间存在密切联系，从而为肿瘤进展的简单、非侵入性替代监测提供了一种可行的方法。这些发现强调了 LOX-1 作为肿瘤进展、迁移、侵袭、转移形成和肿瘤相关新生血管形成的调节剂的作用，提出该受体作为一种有前途的治疗靶点，从而增强了当前的抗肿瘤策略。
