在子宫内膜癌中,EXOSC5通过调节NTN4/整蛋白β1信号轴来维持癌症干细胞活性
Yu-Hao Huang1,2, Wen-Ling Wang2, Po-Hui Wang3,4,5
1Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan.
International journal of biological sciences
|January 2, 2024
概括
外体组分5 (EXOSC5) 通过增加癌症干细胞 (CSC) 活性,促进子宫内膜癌 (EC) 的进展. 准EXOSC5及其下游途径为EC治疗提供了新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 子宫内膜癌 (EC) 的发病率正在上升,特别是在台湾.
- 癌症干细胞 (CSCs) 驱动瘤恶性和耐治疗性.
- 针对CSC对于有效的EC疗法至关重要.
研究的目的:
- 为了研究外体组分5 (EXOSC5) 在子宫内膜癌中的作用.
- 阐明EXOSC5影响癌症干和瘤发生性的分子机制.
主要方法:
- 对EXOSC5表达和预后的癌症基因组图谱 (TCGA) 数据的分析.
- 在EC细胞中对EXOSC5水平的实验操纵 (敲击).
- 评估CSC自我更新,干性标记物 (c-MYC,SOX2) 和瘤性.
- 对NTN4-整蛋白β1-FAK/SRC-c-MYC信号轴的研究.
- 在EC患者组织中对EXOSC5和NTN4的相关性分析.
主要成果:
- 高的EXOSC5mRNA表达与糟糕的EC预后相关.
- 在EXOSC5中,降低了EC-CSC自我更新,干性标志物和瘤性.
- 在EXOSC5的消耗下降了netrin4 (NTN4) 的水平.
- NTN4治疗增强了EC CSC活动,并激活了整体蛋白β1/FAK/SRC/c-MYC通路.
- 在EC组织中,EXOSC5和NTN4表达之间存在正相关性.
结论:
- 通过对NTN4进行上调,EXOSC5促进了EC的进展,NTN4通过整合蛋白β1/FAK/SRC激活了c-MYC通路.
- EXOSC5和NTN4通路代表了子宫内膜癌的潜在诊断和治疗点.
相关概念视频
Cancer Stem Cells and Tumor Maintenance
4.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Cancer Cell Migration through Invadopodia
2.3K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
Metastasis
5.6K
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...
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...
5.6K
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K


