ATP-P2Y2-β-catenin axis promotes cell invasion in breast cancer cells.
ATP-P2Y2-β-catenin axis promotes cell invasion in breast cancer cells.
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DOI：
10.1111/cas.13273
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发表时间：
2017-07
期刊：
影响因子：
5.7
通讯作者：
Fang WG
中科院分区：
文献类型：
--
作者：
Zhang JL;Liu Y;Yang H;Zhang HQ;Tian XX;Fang WG
细胞外腺苷5′-三磷酸（ATP）由活癌细胞分泌或由坏死肿瘤细胞释放，在肿瘤侵袭和转移中发挥重要作用。我们之前的研究表明，体外 ATP 治疗可以通过增强 EMT 过程，通过 ATP 的首选受体 P2Y2 促进对人前列腺癌细胞的侵袭。然而，ATP 和 P2Y2 在乳腺癌中的促侵袭机制仍知之甚少。在这项研究中，我们发现P2Y2在乳腺癌细胞中高表达并与人类乳腺癌转移相关。 ATP可以促进乳腺癌细胞的体外侵袭并增强β-连环蛋白及其下游靶基因CD44、c-Myc和细胞周期蛋白D1的表达，而P2Y2敲低则减弱了体外和体内上述ATP驱动的事件。此外，iCRT14（一种 β-连环蛋白/TCF 复合物抑制剂）还可以在体外抑制 ATP 驱动的迁移和侵袭。这些结果表明 ATP 通过 P2Y2-β-catenin 轴促进乳腺癌细胞侵袭。因此，阻断 ATP-P2Y2-β-catenin 轴可以抑制乳腺癌细胞的侵袭和转移潜力，并可能作为乳腺癌治疗干预的潜在靶点。
Extracellular adenosine 5′‐triphosphate (ATP), secreted by living cancer cells or released by necrotic tumor cells, plays an important role in tumor invasion and metastasis. Our previous study demonstrated that ATP treatment in vitro could promote invasion in human prostate cancer cells via P2Y2, a preferred receptor for ATP, by enhancing EMT process. However, the pro‐invasion mechanisms of ATP and P2Y2 are still poorly studied in breast cancer. In this study, we found that P2Y2 was highly expressed in breast cancer cells and associated with human breast cancer metastasis. ATP could promote the in vitro invasion of breast cancer cells and enhance the expression of β‐catenin as well as its downstream target genes CD44, c‐Myc and cyclin D1, while P2Y2 knockdown attenuated above ATP‐driven events in vitro and in vivo. Furthermore, iCRT14, a β‐catenin/TCF complex inhibitor, could also suppress ATP‐driven migration and invasion in vitro. These results suggest that ATP promoted breast cancer cell invasion via P2Y2‐β‐catenin axis. Thus blockade of the ATP‐P2Y2‐β‐catenin axis could suppress the invasive and metastatic potential of breast cancer cells and may serve as potential targets for therapeutic interventions of breast cancer.