Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells.
Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells.
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Rictor 促进对雷帕霉素不敏感的三阴性乳腺癌细胞的肿瘤进展。
DOI：
10.1016/j.bbrc.2020.08.012
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Oneyama C.
中科院分区：
文献类型：
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作者：
Watanabe R;Miyata M;Oneyama C.
三阴性乳腺癌（TNBC）以激素受体和人表皮生长因子2型受体表达降低为特征，预后较差，缺乏有效的治疗方法。最近，mTOR抑制剂雷帕霉素及其类似物引起了越来越多的关注，并被评估为治疗TNBC的药物，在TNBC中，PI3K/AKT/mTOR通路经常被激活。然而，一些tnbc对这些药物不太敏感。在这项研究中，我们发现TNBC细胞对雷帕霉素的敏感性高度依赖于mTOR的雷帕霉素不敏感伴侣（Rictor）的表达水平，Rictor是mTOR复合物2的关键成分。抑制Rictor表达强烈抑制雷帕霉素不敏感肿瘤细胞的生长。此外，我们发现对Rictor表达的抑制在对mTOR激酶抑制剂产生耐药性的雷帕霉素不敏感细胞中也有效。这些发现表明，Rictor可以作为TNBC中使用雷帕霉素类似物的预测标志物，并强调了开发靶向Rictor治疗TNBC的治疗方法的必要性。
Triple-negative breast cancer (TNBC), characterized by decreased expression of hormone receptors and human epidermal growth factor type 2 receptor, has poor prognosis and lacks effective therapeutics. Recently, the mTOR inhibitor rapamycin and its analogs have attracted growing interests and evaluated as therapeutic agents against TNBC, in which the PI3K/AKT/mTOR pathway is often activated. However, some TNBCs are less sensitive to these drugs. In this study, we found that the sensitivity of TNBC cells to rapamycin was highly dependent on the expression level of rapamycin-insensitive companion of mTOR (Rictor), a key component of the mTOR complex 2. Repression of the Rictor expression strongly suppressed the growth of rapamycin-insensitive tumor cells. Furthermore, we showed that the suppression of Rictor expression was also effective in rapamycin-insensitive cells that had acquired resistance to mTOR kinase inhibitors. These findings indicate that Rictor can be a predictive marker for the use of rapamycin analogs in TNBC and highlight the need to develop therapeutics targeting Rictor in the treatment of TNBC.
影响因子：
11.2
作者：
Werfel TA;Wang S;Jackson MA;Kavanaugh TE;Joly MM;Lee LH;Hicks DJ;Sanchez V;Ericsson PG;Kilchrist KV;Dimobi SC;Sarett SM;Brantley-Sieders DM;Cook RS;Duvall CL
通讯作者：
Duvall CL
影响因子：
3.4
作者：
C. Vicier;M. Dieci;F. André
通讯作者：
C. Vicier;M. Dieci;F. André
DOI：
10.1016/j.ddstr.2009.12.001
发表时间：
2009
期刊：
Drug discovery today. Therapeutic strategies
影响因子：
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作者：
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