ATX-LPA生物学功能及其在乳腺癌中的研究进展

Biological function of ATX-LPA axis and its progress in cancer

目的总结近年来关于自分泌运动因子-溶血磷脂酸(autotaxin-lysophosphatidic acid,ATX-LPA)生物学功能及其在乳腺癌中的研究进展。方法应用PubMed和CNKI期刊全文数据库检索系统,以"乳腺肿瘤、自分泌运动因子、溶血磷脂酸"为关键词,检索2006-01-2014-04相关文献。纳入标准:1)ATX-LPA生物学功能的相关研究;2)ATX-LPA在乳腺癌中的相关性研究。排除标准:非乳腺癌和非ATX-LPA。根据纳入标准和排除标准,符合分析的文献45篇。结果 ATX与LPA组成ATX-LPA生物轴,通过作用于特异的G蛋白耦联受体(G-protein-coupled receptor,GPCR)介导信号通路的转导,在乳腺癌发生、转移、化疗耐药、内分泌耐药和放疗抵抗中发挥重要的生物学功能,靶向ATX-LPA生物轴有望为乳腺癌治疗提供新的策略。ATX-LPA生物轴在乳腺癌中的作用分子机制、针对这些机制中某些靶点的抑制剂或单克隆抗体在基础实验和(或)临床试验中取得一定程度的进展。结论 ATX-LPA在乳腺癌发生、转移及耐药中的重要作用已经得到证实,具体机制需要更多的基础研究来揭示,靶向ATX-LPA有望为乳腺癌治疗提供新的选择,提高乳腺癌治疗疗效。

OBJECTIVE To summarize the recent advances in the biological function of ATX-LPA axis and its association with breast cancer.METHODS The PubMed and CNKI database from Jan.2006 to Apr.2014 were filtered by search teams ＂ breast cancer,autotaxin,lysophosphatidic acid＂.Exclusion criteria：non breast cancer and non ATX-LPA.Inclusion criterion：Recent literature about the biological function of ATX-LPA axis.Latest advances regards to some of the key findings of ATX-LPA signalling axis in breast cancer.Totally 45 literatures were enrolled in the study according to the criterions.RESULTS The ATX-LPA signaling axis acts on a series of high-affinity cell surface G protein-coupled receptors （GPCRs）,leading to diverse biological actions.Many subsequent studies have combined to establish an important function for the ATX-LPA axis in mammary tumourigenesis,metastasis and drug resistance,suggesting that the ATX-LPA signalling axis is a novel target in breast cancer.The focus of researches now turn to understanding the mechanisms by which ATX and LPA promote mammary tumourigenesis,metastasis and and drug resistance.Researches about the inhibitors and monoclonal antibodies in the above-mentioned mechanisms have achieved some improvements in laboratory and clinical studies.CONCLUSIONS The biological function of ATX-LPA signaling axis in mammary tumourigenesis,metastasis and drug resistance has been confirmed,more laboratory studies are needed to provide powerful evidence to clarify detailed mechanism between ATX-LPA signaling axis and breast cancer.Targeting the ATX-LPA signalling axis for drug development may further improve the outcomes in patients of breast cancer.