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研究分野生物医学と臨床科学腫瘍学とがん発生予測・予測マーカー
ヒッポ経路エフェクターYAPとTAZの周周周活性化により,マウスの肝がんが抑制される.

ヒッポ経路エフェクターYAPとTAZの周周周活性化により,マウスの肝がんが抑制される.

Iván M Moya ^1,2, Stéphanie A Castaldo ¹, Laura Van den Mooter ¹, Soheil Soheily ¹, Leticia Sansores-Garcia ¹, Jelle Jacobs ³, Inge Mannaerts ⁴, Jun Xie ¹, Elisabeth Verboven ¹, Hanne Hillen ¹, Ana Algueró-Nadal ¹, Ruchan Karaman ¹, Matthias Van Haele ⁵, Weronika Kowalczyk ¹, Maxime De Waegeneer ³, Stefaan Verhulst ⁴, Panagiotis Karras ⁶, Leen van Huffel ¹, Lars Zender ^7,8,9, Jean-Christophe Marine ⁶, Tania Roskams ⁵, Randy Johnson ¹⁰, Stein Aerts ³, Leo A van Grunsven ⁴, Georg Halder ¹¹

Iván M Moya ^1,2, Stéphanie A Castaldo ¹, Laura Van den Mooter ¹

¹VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, Leuven, Belgium.
²Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, Quito, Ecuador.
³VIB Center for Brain and Disease Research and KU Leuven Center for Human Genetics, University of Leuven, Leuven, Belgium.
⁴Liver Cell Biology Research Group, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
⁵Department of Imaging and Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
⁶Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology and Department of Oncology, KU Leuven, Leuven, Belgium.
⁷Department of Medical Oncology and Pneumology, University Hospital Tuebingen, 72076 Tuebingen, Germany.
⁸German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁹iFIT Cluster of Excellence EXC 2180 "Image Guided and Functionally Instructed Tumour Therapies," University of Tuebingen, Tuebingen, Germany.
¹⁰Department of Cancer Biology, Program in Cancer Biology, Graduate School for Biological Sciences GSBS, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, Leuven, Belgium. georg.halder@vib.be.

⁰VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, Leuven, Belgium.

Clinical Neuroscience (new York, N.y.) +

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2019年11月23日

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PubMedで要約を見る

まとめ

この要約は機械生成です。

ヒッポの経路にある YAPとTAZのタンパク質は腫瘍を駆動するだけでなく抑制します腫瘍細胞ではなく周囲の正常細胞での活動が細胞の競争によって腫瘍の成長や衰退を決定します

科学分野

細胞生物学
腫瘍学
分子生物学

背景

YAPとTAZの転写共同活性化剤を含むHippoシグナル伝達経路は,様々な実験モデルで腫瘍の進行の主要な原動力として認識されています.
しかし,腫瘍微環境におけるYAPとTAZの正確な役割とその潜在的な腫瘍抑制機能は,まだ完全に理解されていません.

研究の目的

肝臓腫瘍の成長と衰退における YAP と TAZ の二重の役割を調査する.
腫瘍細胞の生存と消去に対する YAP と TAZ 活性の影響を調査する.

主な方法

ヒッポシグナル経路が肝臓腫瘍に与える影響をマウスモデルで調べました
肝臓腫瘍を囲む肝細胞におけるYAPとTAZの発現と活性を遺伝子操作した.
変化したYAPとTAZ活性に対する腫瘍の成長,回帰,および細胞生存率の評価

主要な成果

肝臓腫瘍の隣接する肝細胞におけるYAPとTAZの除去は,腫瘍の成長を加速させ,この文脈で腫瘍抑制作用を示す.
周周肝細胞におけるYAPの過剰活性化により,原発性肝臓腫瘍とメラノーマの転移が減少した.
YAPとTAZに対する腫瘍細胞の生存は,周囲の非腫瘍組織におけるこれらのタンパク質の活性に依存していた.

結論

YAPとTAZは文脈に依存する機能を示し,周周微環境で腫瘍抑制剤として作用する.
腫瘍細胞と周囲の肝細胞の間の相対的なYAPとTAZ活動は,腫瘍の運命に影響する.
細胞の競争は,YAPとTAZによって媒介され,肝臓の微小環境内の腫瘍細胞を排除する潜在的なメカニズムです.

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