論文 - 詳細
| RRC ID | 74552 |
|---|---|
| 著者 | Nitta S, Kandori S, Tanaka K, Sakka S, Siga M, Nagumo Y, Negoro H, Kojima T, Mathis BJ, Shimazui T, Miyamoto T, Matsuzaka T, Shimano H, Nishiyama H. |
| タイトル | ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma. |
| ジャーナル | Cancer Sci |
| Abstract |
Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long-chain fatty acid (ELOVL) family enzymes catalyze fatty acid elongation, and ELOVL5 is indispensable for PUFAs elongation, but its role in RCC progression remains unclear. Here, we show that higher levels of ELOVL5 correlate with poor RCC clinical prognosis. Liquid chromatography/electrospray ionization-tandem mass spectrometry analysis showed decreases in ELOVL5 end products (arachidonic acid and eicosapentaenoic acid) under CRISPR/Cas9-mediated knockout of ELOVL5 while supplementation with these fatty acids partially reversed the cellular proliferation and invasion effects of ELOVL5 knockout. Regarding cellular proliferation and invasion, CRISPR/Cas9-mediated knockout of ELOVL5 suppressed the formation of lipid droplets and induced apoptosis via endoplasmic reticulum stress while suppressing renal cancer cell proliferation and in vivo tumor growth. Furthermore, CRISPR/Cas9-mediated knockout of ELOVL5 inhibited AKT Ser473 phosphorylation and suppressed renal cancer cell invasion through chemokine (C-C motif) ligand-2 downregulation by AKT-mTOR-STAT3 signaling. Collectively, these results suggest that ELOVL5-mediated fatty acid elongation promotes not only cellular proliferation but also invasion in RCC. |
| 巻・号 | 113(8) |
| ページ | 2738-2752 |
| 公開日 | 2022-8-1 |
| DOI | 10.1111/cas.15454 |
| PMID | 35670054 |
| PMC | PMC9357625 |
| MeSH | Acetyltransferases / genetics Acetyltransferases / metabolism Carcinoma, Renal Cell* / genetics Carcinoma, Renal Cell* / pathology Cell Proliferation / genetics Fatty Acid Elongases* / genetics Fatty Acids Humans Kidney Neoplasms* / genetics Kidney Neoplasms* / pathology Proto-Oncogene Proteins c-akt |
| IF | 4.966 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |