Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells
| Autor: | Risayo Watanabe, Mamiko Miyata, Chitose Oneyama |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Biophysics Triple Negative Breast Neoplasms Biochemistry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Humans Medicine Receptor Protein Kinase Inhibitors Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Triple-negative breast cancer Sirolimus Predictive marker business.industry Kinase TOR Serine-Threonine Kinases digestive oral and skin physiology Cell Biology Up-Regulation Gene Expression Regulation Neoplastic Rapamycin-Insensitive Companion of mTOR Protein 030104 developmental biology Drug Resistance Neoplasm Tumor progression Hormone receptor 030220 oncology & carcinogenesis Cancer research Female business |
| Zdroj: | Biochemical and Biophysical Research Communications. 531:636-642 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.08.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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