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Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells

Watanabe, Risayo ; Miyata, Mamiko ; Oneyama, Chitose

Biochemical and biophysical research communications, 2020-10, Vol.531 (4), p.636-642 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells
Autor: Watanabe, Risayo ; Miyata, Mamiko ; Oneyama, Chitose
Assuntos: Cell Line, Tumor ; Drug Resistance, Neoplasm - drug effects ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Protein Kinase Inhibitors - pharmacology ; Rapamycin ; Rapamycin-Insensitive Companion of mTOR Protein - genetics ; Rapamycin-Insensitive Companion of mTOR Protein - metabolism ; Rictor ; Sirolimus - pharmacology ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Triple Negative Breast Neoplasms - drug therapy ; Triple Negative Breast Neoplasms - genetics ; Triple Negative Breast Neoplasms - pathology ; Triple-negative breast cancer ; Up-Regulation
É parte de: Biochemical and biophysical research communications, 2020-10, Vol.531 (4), p.636-642
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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. •Rictor is upregulated in rapamycin-insensitive TNBC cells.•Rictor promotes tumor progression in rapamycin-insensitive TNBC cells.•mTOR kinase inhibitors effectively inhibit growth of Rictor-upregulated TNBC cells.•Rictor expression is retained in TNBC cells resistant to mTOR kinase inhibitors.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells

Watanabe, Risayo ; Miyata, Mamiko ; Oneyama, Chitose

United States: Elsevier Inc

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