相关实验视频

Updated: Jan 18, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

核气体胺E驱动内甲素-1诱导的转移性进展,独立于热致死

Celia Roman¹, Valentina Caprara¹, Piera Tocci¹

¹Preclinical Models and New Therapeutic Agents Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Regina Elena National Cancer Institute, Rome, Italy.

Cell death & disease

|January 16, 2026

概括

加斯德明E (GSDME) 通过调节ZEB1的基因表达来驱动卵巢癌转移,独立于热. 用抗体向内甲素-1受体A (ET_AR) 途径可以减少转移,并改善高度血清性卵巢癌患者的结果.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

转移性扩散是高度血清性卵巢癌 (HG-SOC) 患者结局的关键决定因素.
驱动HG-SOC转移的分子机制尚不完全理解.
气体皮膜 (GSDMs) 已成为癌症的关键调节剂,具有超越热的新功能.

研究的目的:

研究 GSDME 在 HG-SOC 转移中的作用.
阐明GSDME,内甲素-1 (ET-1) /ET-1受体A (ET_AR) 信号传递和HG-SOC中的上皮-介质细胞过渡 (EMT) 之间的相互作用.
探索针对ET_AR/GSDME轴的治疗潜力.

主要方法:

对HG-SOC组织中GSDME表达的分析以及与EMT标记物和ET_AR表达的相关性.
通过ET-1通过EMT因子ZEB1和ZEB2.2发出信号来研究GSDME的转录调节.
评估GSDME在调节EMT和炎症基因中的核转位和转录活性.
评估 GSDME 枯竭,ZEB1 抑制和 ET_AR 阻断对 HG-SOC 转移性表型 in vitro 和 in vivo 的影响.

主要成果:

GSDME上调与HG-SOC中的EMT和ET_AR表达相关.
ET-1信号诱导通过ZEB1/ZEB2诱导GSDME转录,促进EMT.
核GSDME与ZEB1相互作用,以调节E-cadherin,vimentin和IL-6的表达.
阻止ET_AR或消耗GSDME/ZEB1可以抑制ET-1-诱导的EMT和炎症反应.
ET-1受体对抗剂通过破坏GSDME/ZEB1复合体来减少HG-SOC转移性特征.

结论:

在HG-SOC转移中,GSDME作为核转录调节器独立于热的功能.
在ET_AR/GSDME/ZEB1轴驱动的攻击性行为和不良预后介质细胞 HG-SOC.
用对抗剂准ET_AR是一种有希望的治疗策略,可以减少HG-SOC的转移负担.

更多相关视频

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Published on: June 16, 2018

相关概念视频

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

Metastasis

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...