論文 - 詳細
| RRC ID | 83137 |
|---|---|
| 著者 | Tsutsumi K, Nohara A, Tanaka T, Murano M, Miyagaki Y, Ohta Y. |
| タイトル | FilGAP regulates tumor growth in Glioma through the regulation of mTORC1 and mTORC2. |
| ジャーナル | Sci Rep |
| Abstract |
The mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that forms the two different protein complexes, known as mTORC1 and mTORC2. mTOR signaling is activated in a variety of tumors, including glioma that is one of the malignant brain tumors. FilGAP (ARHGAP24) is a negative regulator of Rac, a member of Rho family small GTPases. In this study, we found that FilGAP interacts with mTORC1/2 and is involved in tumor formation in glioma. FilGAP interacted with mTORC1 via Raptor and with mTORC2 via Rictor and Sin1. Depletion of FilGAP in KINGS-1 glioma cells decreased phosphorylation of S6K and AKT. Furthermore, overexpression of FilGAP increased phosphorylation of S6K and AKT, suggesting that FilGAP activates mTORC1/2. U-87MG, glioblastoma cells, showed higher mTOR activity than KINGS-1, and phosphorylation of S6K and AKT was not affected by suppression of FilGAP expression. However, in the presence of PI3K inhibitors, phosphorylation of S6K and AKT was also decreased in U-87MG by depletion of FilGAP, suggesting that FilGAP may also regulate mTORC2 in U-87MG. Finally, we showed that depletion of FilGAP in KINGS-1 and U-87MG cells significantly reduced spheroid growth. These results suggest that FilGAP may contribute to tumor growth in glioma by regulating mTORC1/2 activities. |
| 巻・号 | 13(1) |
| ページ | 20956 |
| 公開日 | 2023-12-8 |
| DOI | 10.1038/s41598-023-47892-1 |
| PII | 10.1038/s41598-023-47892-1 |
| PMID | 38065968 |
| PMC | PMC10709582 |
| MeSH | GTPase-Activating Proteins* / metabolism Glioma* / metabolism Glioma* / pathology Humans Mechanistic Target of Rapamycin Complex 1 / metabolism Mechanistic Target of Rapamycin Complex 2 / metabolism Multiprotein Complexes / metabolism Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Proto-Oncogene Proteins c-akt* / metabolism TOR Serine-Threonine Kinases / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMV5-Flag-Sin1 (RDB20790) pMAL-c2X-Sin1 (RDB20791) |