癌細胞の移動中の核膜の破裂と修復

Celine M Denais¹, Rachel M Gilbert¹, Philipp Isermann¹

¹Nancy E. and Peter C. Meinig School of Biomedical Engineering and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.

Science (New York, N.Y.)

|March 26, 2016

まとめ

癌細胞は核を変形させ組織に侵入し核膜に損傷を与えますトランスポートIII (ESCRTIII) 機械に必要な内体分離複合体は,この損傷を修復し,転移時に細胞の生存を可能にします.

科学分野:

細胞生物学
癌の研究
バイオ物理学

背景:

癌の転移は腫瘍細胞が狭い組織空間を移動することを意味します
この移動には細胞と核の大きな変形が必要です
細胞のホメオスタシスを維持するために核包膜の整合性は極めて重要です

研究の目的:

哺乳類の腫瘍細胞移動に対する閉じ込められた微小環境の影響を調査する.
細胞移動中の核膜 (NE) の損傷と修復のメカニズムを理解する.
NEの整合性を回復する細胞機構を特定する.

主な方法:

哺乳類の腫瘍細胞の移動に関するインビトロおよびインビボの研究.
核変形とNEの整合性を観察するための顕微鏡技術.
核細胞質の交換とDNA損傷の分析
核ラミンの役割とESCRT IIIの仕組みを調査する.

主要な成果:

移動中の核変形は,NEの局所的整合性の喪失につながった.
NE破裂は制御不能な核細胞質の交換,クロマチンヘルニア,DNA損傷を引き起こした.
NE破裂の頻度は,細胞の閉じ込め度が増え,核ラミンのレベルが低下した.
トランスポートIII (ESCRTIII) 機械に必要な内体分離複合体は,NEの整合性を回復するために使用された.

結論:

狭い空間を通る細胞の移動は核膜に相当な物理的ストレスを与える.
NEとDNAの損傷の効率的な修復は,転移中の癌細胞の生存に不可欠です.
ESCRT IIIシステムは,物理的なストレス下での核の完全性を維持する上で重要な役割を果たします.

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