Integrin α6/Akt/Erk signaling is essential for human breast cancer resistance to radiotherapy.
Integrin α6/Akt/Erk signaling is essential for human breast cancer resistance to radiotherapy.
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整合素 α 6/Akt/Erk 信号传导对于人类乳腺癌对放疗的抵抗力至关重要
DOI：
10.1038/srep33376
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发表时间：
2016-09-14
影响因子：
4.6
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Hu T;Zhou R;Zhao Y;Wu G
整合素α6（ITGA 6）是一种跨膜糖蛋白粘附受体蛋白，在许多类型的肿瘤中广泛上调，并促进癌细胞的迁移和侵袭。然而，ITGA 6相关信号网络在乳腺癌放射敏感性中的作用尚未被描述。使用蛋白质印迹分析检测ITGA 6在人乳腺癌和正常乳腺细胞系中的表达。我们还通过殖民地形成实验、细胞周期分析、细胞凋亡实验和免疫荧光分析，探讨了ITGA 6在乳腺癌辐射敏感性调节中的作用。结果显示，ITGA 6在乳腺癌细胞中的蛋白和mRNA表达水平均高于正常细胞。ITGA 6通过改变细胞凋亡、DNA损伤修复和细胞周期调控来保护乳腺癌细胞对放疗的反应。此外，ITGA 6通过PI 3 K/Akt和MEK/Erk信号通路增强辐射抗性。此外，过表达ITGA 6促进细胞的辐射抗性，并且这种作用被PI 3 K抑制剂LY 294002和MEK抑制剂U 0126中和。总之，这些研究结果表明，ITGA 6可能参与了辐射抗性的机制，并且ITGA 6可能是旨在克服乳腺癌辐射抗性的治疗的潜在靶点。
Integrin α6 (ITGA6), a transmembrane glycoprotein adhesion receptor protein, is widely upregulated in many types of tumors and promotes migration and invasion in cancer cells. However, the role that the ITGA6-associated signaling network plays in radiosensitivity in breast cancer has not been described. The expression of ITGA6 was examined in human breast cancer and normal breast cell lines using western blot analysis. We also explored the role of ITGA6 in the regulation of radiation sensitivity in breast cancer using the colony formation assays, cell cycle analyses, apoptosis assays and immunofluorescence analyses. The results showed that the protein and mRNA expression levels of ITGA6 was higher in breast cancer cells than in normal cells. ITGA6 protectived responses to radiotherapy in breast cancer cells by altering cell apoptosis, DNA damage repair and cell-cycle regulation. Furthermore, ITGA6 enhanced radiation resistance via PI3K/Akt and MEK/Erk signaling. In addition, overexpressing ITGA6 promoted radiation resistance in cells, and this effect was neutralized by the PI3K inhibitor LY294002 and MEK inhibitor U0126. Taken together, these findings indicate that ITGA6 might be involved in a mechanism that underlies radiation resistance and that ITGA6 could be a potential target for therapies aimed at overcoming radiation resistance in breast cancer.
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