ディブチルフタレットは,TIMP1/PI3K/AKTシグナリング軸経由でCOAD細胞の成長と移動を促進する.
PubMedで要約を見る
まとめ
この要約は機械生成です。ディブチルフラート (DBP) 曝露は結腸がん細胞の成長と移転を促進する. これらの効果をPI3K/AKT経路で駆動し,DBPを指示します.
科学分野
- 環境毒理学
- 癌 生物学
- 分子腫瘍学
背景
- ディブチルフタレート (DBP) は,消費製品に含まれる一般的な可塑剤です.
- DBPの曝露は悪性腫瘍の増殖と関連している.
- 大腸腺がん (COAD) の進行におけるDBPの特定の役割については,さらなる調査が必要である.
研究 の 目的
- 結腸がん細胞の進行に対する DBP の影響を調査する.
- DBP媒介によるCOAD発現に関与する重要な遺伝子と経路を特定する.
- DBP誘発のCOADの予後モデルを開発し,検証する.
主な方法
- 遺伝子識別のためのコックスとLASSOの回帰分析
- 多遺伝子予測リスクモデルの開発と検証
- Caco-2およびHT-29細胞に対するDBPのインビトロ評価 (増殖,コロニー形成,移動).
- TIMP-1とPI3K/AKT経路を含む分子メカニズムの探索
主要な成果
- DBPの曝露は,大腸がん細胞の増殖,コロニー形成,移動を著しく増加させた.
- TIMP-1を鍵となる遺伝子として特定した10遺伝子予測モデルが構築された.
- TIMP-1はDBPによって上調され,DBP濃度と相関していた.
- TIMP-1のノックダウンにより,DBP誘発の細胞増殖とPI3K/ AKT経路の活性化が抑制されました.
結論
- DBPはTIMP- 1の調節とPI3K/ AKT経路の活性化によって結腸がん細胞の進行を促進する.
- TIMP- 1は,大腸がんにおけるDBPの癌誘発作用の媒介として作用する.
- この研究は,DBPの遺伝子毒性とその大腸がんへの影響を理解するための基礎を提供します.
関連する概念動画
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...

