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自主分泌酶-溶血磷脂酸轴:促进癌症发展和可能的治疗意义。

Autotaxin-Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications.

机构信息

Medical Oncology Unit, National Institute of Gastroenterology, IRCCS "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.

Medical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy.

出版信息

Int J Mol Sci. 2024 Jul 15;25(14):7737. doi: 10.3390/ijms25147737.

Abstract

Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase () family; it is encoded by the gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1-6). The ATX-LPA axis is involved in various physiological and pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, and obesity. However, significant research also reported its connection to carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, and therapeutic resistance. Moreover, several studies suggested ATX and LPA as relevant biomarkers and/or therapeutic targets. In this review of the literature, we aimed to deepen knowledge about the role of the ATX-LPA axis as a promoter of cancer development, progression and invasion, and therapeutic resistance. Finally, we explored its potential application as a prognostic/predictive biomarker and therapeutic target for tumor treatment.

摘要

自分泌酶(ATX)是核苷酸焦磷酸酶/磷酸二酯酶()家族的成员;它由基因编码。ATX 是一种分泌性糖蛋白,可催化溶血磷脂酰胆碱水解为溶血磷脂酸(LPA)。LPA 通过与至少六种 G 蛋白偶联受体(LPAR1-6)相互作用,负责各种信号通路的转导。ATX-LPA 轴参与多种生理和病理过程,如血管生成、胚胎发育、炎症、纤维化和肥胖。然而,大量研究还报道了其与致癌作用、免疫逃逸、转移、肿瘤微环境、癌症干细胞和治疗耐药性的联系。此外,一些研究表明 ATX 和 LPA 可作为相关的生物标志物和/或治疗靶点。在这篇文献综述中,我们旨在深入了解 ATX-LPA 轴作为癌症发展、进展和侵袭以及治疗耐药性促进因子的作用。最后,我们探讨了其作为肿瘤治疗的预后/预测生物标志物和治疗靶点的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd2f/11277072/6556f23d4b9b/ijms-25-07737-g001.jpg

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