腎臓系因子PAX8は,腎臓がんにおける腫瘍性シグナリングを制御する
Saroor A Patel1,2, Shoko Hirosue1, Paulo Rodrigues1
1MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
Nature
|June 8, 2022
まとめ
血統転写因子PAX8は,クリアセル腎臓細胞癌 (ccRCC) の発症に不可欠である. 遺伝的および体的変異の両方の腫瘍的シグナル伝達を媒介し,組織特有のがんリスクを説明します.
科学分野:
- 腫瘍学
- 遺伝学
- 分子生物学
背景:
- がん変異は強い組織選択性を表しますが,その背後にあるメカニズムは完全に理解されていません.
- 明らかに細胞性腎臓がん (ccRCC) は,遺伝的要因が知られている一般的な腎臓がんである.
- 組織特異的な癌の発症における系統転写因子の役割は,活発な研究分野である.
研究 の 目的:
- ccRCCの腫瘍性シグナル伝達における血統転写因子ペアリングボックス8 (PAX8) の役割を調査する.
- PAX8がccRCCにおける遺伝的変異と関連した組織特異的ながんリスクをどのように媒介するかを明らかにする.
- ccRCCの病原性におけるPAX8,VHL損失,およびHIF2Aの相互作用を理解する.
主な方法:
- 実験モデル
- 機能的ゲノミクス
- 患者のサンプル分析
- クロマチン 免疫 プレシピテーション 測定
- 遺伝子発現分析
主要な成果:
- ゲルムライン変種 (rs7948643) と体内のVHL不活性化によって引き起こされるccRCCにおける腫瘍性シグナル伝達にはPAX8が必要である.
- 低酸素誘導因子2α (HIF2A) は,CCND1増強剤を含むPAX8結合増強剤に優先的に誘導される.
- rs7948643のccRCC保護性アレルCはPAX8結合とCCND1発現を阻害する.
- PAX8に依存したプログラムは,ccRCCの転移においてMYC発現に併用されます.
結論:
- PAX8のような血統転写因子は,ccRCCにおける腫瘍性シグナル伝達の重要なメディエーターである.
- PAX8は,体内および遺伝的遺伝子変異の両方の組織特異的な癌リスクを与える上で重要な役割を果たします.
- PAX8の役割を理解すると,ccRCCの発達と潜在的な治療戦略の洞察が得られます.
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