Syndecan 1は,臓がんにおけるマクロピノサイトーシスの重要な媒介体である

Wantong Yao^1,2, Johnathon L Rose¹, Wei Wang³

¹Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nature

|March 29, 2019

まとめ

臓がん細胞はKRAS*信号に依存し,その表面上のシンデカン1 (SDC1) を上調する. SDC1をターゲットにすることで栄養素の吸収を妨害することでこの攻撃的な癌の治療に新たな戦略が提供されるかもしれません

科学分野:

腫瘍学
分子生物学
ガンゲノミクス

背景:

管腺がん (PDAC) の前見は悪で,5年生存率は8%である.
腫瘍性KRAS (KRAS*) はPDAC症例の90%以上を誘発しますが,それを標的とするだけで再発が起こり,同消滅戦略が必要になります.
細胞表面プロテオーム (surfaceome) は腫瘍性シグナル伝達に不可欠であるが,PDACにおけるKRAS*によるその調節は十分に理解されていない.

研究の目的:

PDACにおけるKRAS*依存の表面オーム変異を発見するための機能的なプラットフォームを開発する.
KRAS*シグナルによるPDACの新たな脆弱性を特定する.

主な方法:

無偏見で機能的な標的発見プラットフォームを使用して,PDAC表面群のKRAS*依存変化を分析した.
PDAC細胞の成長と腫瘍の維持における特定された表面タンパク質の役割を調査した.

主要な成果:

細胞表面でKRAS*によって上調されるタンパク質として,シンデカン1 (SDC1 又はCD138として知られる) を特定した.
細胞表面SDC1は,PDACの成長を促進する重要な代謝経路であるマクロピノサイトーシスの調節に不可欠であることを実証した.
PDACの維持と進行における SDC1の重要な役割が確認された.

結論:

KRAS*シグナル伝達とPDACにおける栄養素回収経路に関与する標的分子であるSDC1との間にメカニズム的なリンクが確立された.
がん特有の脆弱性を特定するための実行可能な戦略として,検証された腫瘍遺伝子駆動の表面積アノテーション.

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