論文 - 詳細
| RRC ID | 82846 |
|---|---|
| 著者 | Ohya S, Kito H, Kajikuri J, Yamaguchi Y, Matsui M. |
| タイトル | Transcriptional Up-Regulation of FBXW7 by KCa1.1 K+ Channel Inhibition through the Nrf2 Signaling Pathway in Human Prostate Cancer LNCaP Cell Spheroid Model. |
| ジャーナル | Int J Mol Sci |
| Abstract |
The tumor suppressor gene F-box and WD repeat domain-containing (FBXW) 7 reduces cancer stemness properties by promoting the protein degradation of pluripotent stem cell markers. We recently demonstrated the transcriptional repression of FBXW7 by the three-dimensional (3D) spheroid formation of several cancer cells. In the present study, we found that the transcriptional activity of FBXW7 was promoted by the inhibition of the Ca2+-activated K+ channel, KCa1.1, in a 3D spheroid model of human prostate cancer LNCaP cells through the Akt-Nrf2 signaling pathway. The transcriptional activity of FBXW7 was reduced by the siRNA-mediated inhibition of the CCAAT-enhancer-binding protein C/EBP δ (CEBPD) after the transfection of miR223 mimics in the LNCaP spheroid model, suggesting the transcriptional regulation of FBXW7 through the Akt-Nrf2-CEBPD-miR223 transcriptional axis in the LNCaP spheroid model. Furthermore, the KCa1.1 inhibition-induced activation of FBXW7 reduced (1) KCa1.1 activity and protein levels in the plasma membrane and (2) the protein level of the cancer stem cell (CSC) markers, c-Myc, which is a molecule degraded by FBXW7, in the LNCaP spheroid model, indicating that KCa1.1 inhibition-induced FBXW7 activation suppressed CSC conversion in KCa1.1-positive cancer cells. |
| 巻・号 | 25(11) |
| 公開日 | 2024-5-30 |
| DOI | 10.3390/ijms25116019 |
| PII | ijms25116019 |
| PMID | 38892210 |
| PMC | PMC11172474 |
| MeSH | Cell Line, Tumor F-Box-WD Repeat-Containing Protein 7* / genetics F-Box-WD Repeat-Containing Protein 7* / metabolism Gene Expression Regulation, Neoplastic* Humans Intermediate-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors Intermediate-Conductance Calcium-Activated Potassium Channels / genetics Intermediate-Conductance Calcium-Activated Potassium Channels / metabolism Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism Male MicroRNAs / genetics MicroRNAs / metabolism NF-E2-Related Factor 2* / genetics NF-E2-Related Factor 2* / metabolism Prostatic Neoplasms* / genetics Prostatic Neoplasms* / metabolism Prostatic Neoplasms* / pathology Proto-Oncogene Proteins c-akt / metabolism Signal Transduction* Spheroids, Cellular* / metabolism Up-Regulation |
| IF | 4.556 |
| リソース情報 | |
| ヒト・動物細胞 | LNCap.FGC(RCB2144) |