Insulin-like growth factor-1 signaling is responsible for cathepsin G-induced aggregation of breast cancer MCF-7 cells.
Insulin-like growth factor-1 signaling is responsible for cathepsin G-induced aggregation of breast cancer MCF-7 cells.
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DOI：
10.1111/cas.13286
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发表时间：
2017-08
期刊：
影响因子：
5.7
通讯作者：
Yui S
中科院分区：
文献类型：
--
作者：
Morimoto-Kamata R;Yui S
组织蛋白酶G（CG）是一种中性粒细胞丝氨酸蛋白酶，在依赖于E-钙粘蛋白和CG酶活性的过程中诱导人乳腺癌MCF-7细胞的细胞迁移和多细胞聚集。虽然这些肿瘤细胞聚集体可引起肿瘤栓塞，其可代表血管内生长和外渗到周围组织中，导致转移，但该过程的分子机制仍缺乏表征。在这项研究中，我们的目的是确定在CG介导的细胞聚集刺激过程中触发的信号通路。对含有约90种分子靶向药物的化合物库进行筛选，发现这一过程受到胰岛素样生长因子-1（IGF-1）受体（IGF-1 R）特异性激酶抑制剂OSI-906以及多激酶抑制剂阿西替尼和舒尼替尼的抑制。能够检测49种不同受体酪氨酸激酶的酪氨酸磷酸化的抗体阵列分析和免疫沉淀研究的结果表明，IGF-1 R在CG处理后被磷酸化。值得注意的是，通过用特异性抗体处理的IGF-1 R中和或通过siRNA转染的IGF-1 R表达沉默抑制了细胞聚集。此外，CG处理MCF-7细胞导致IGF-1向培养基中的释放增加24小时，而抗体介导的IGF-1中和部分阻止CG诱导的细胞聚集。这些结果表明，自分泌IGF-1信号传导是CG诱导的细胞聚集的部分原因。
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF‐7 cells in a process that is dependent on E‐cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG‐mediated stimulation of cell aggregation. Screening of a library of compounds containing approximately 90 molecular‐targeting drugs revealed that this process was suppressed by the insulin‐like growth factor‐1 (IGF‐1) receptor (IGF‐1R)‐specific kinase inhibitor OSI‐906, as well as the multikinase inhibitors axitinib and sunitinib. Antibody array analysis, which is capable of detecting tyrosine phosphorylation of 49 distinct receptor tyrosine kinases, and the results of immunoprecipitation studies indicated that IGF‐1R is phosphorylated in response to CG treatment. Notably, IGF‐1R neutralization via treatment with a specific antibody or silencing of IGF‐1R expression through siRNA transfection suppressed cell aggregation. Furthermore, CG treatment of MCF‐7 cells resulted in increased release of IGF‐1 into the medium for 24 h, while antibody‐mediated IGF‐1 neutralization partially prevented CG‐induced cell aggregation. These results demonstrate that autocrine IGF‐1 signaling is partly responsible for the cell aggregation induced by CG.
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影响因子：
2.9
作者：
Anantha, NV;Azam, M;Sheardy, RD
通讯作者：
Sheardy, RD
DOI：
10.1080/110241502321116541
发表时间：
2002-01-01
期刊：
EUROPEAN JOURNAL OF SURGERY
影响因子：
--
作者：
Doi, K;Horiuchi, T;Tanaka, K
通讯作者：
Tanaka, K
影响因子：
4.1
作者：
Garuti, Laura;Roberti, Marinella;Bottegoni, Giovanni
通讯作者：
Bottegoni, Giovanni
影响因子：
82.9
作者：
Houghton, A. McGarry;Rzymkiewicz, Danuta M.;Ji, Hongbin;Gregory, Alyssa D.;Egea, Eduardo E.;Metz, Heather E.;Stolz, Donna B.;Land, Stephanie R.;Marconcini, Luiz A.;Kliment, Corrine R.;Jenkins, Kimberly M.;Beaulieu, Keith A.;Mouded, Majd;Frank, Stuart J.;Wong, Kwok K.;Shapiro, Steven D.
通讯作者：
Shapiro, Steven D.
影响因子：
8
作者：
Alpaugh, ML;Tomlinson, JS;Barsky, SH
通讯作者：
Barsky, SH