同时针对细胞外囊泡贩运和TGF-β受体激酶活性,阻断信号过活化和转移的信号
Adilson Fonseca Teixeira1,2, Yanhong Wang1, Josephine Iaria1,2
1Department of Surgery (The Royal Melbourne Hospital), The University of Melbourne, Parkville, VIC, Australia.
Signal transduction and targeted therapy
|December 17, 2023
概括
小细胞外囊泡 (sEVs) 通过增强转化生长因子β (TGF-β) 信号传递,驱动乳腺癌转移. 抑制sEV分泌提供了一种新的治疗策略,以使TGF-β水平正常化并减少癌症的传播.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症转移 癌症转移
背景情况:
- 转化生长因子β (TGF-β) 信号传递是癌症转移的关键驱动力,但直接抑制的治疗成功有限.
- 更深入地了解TGF-β生物学对于开发有效的抗转移疗法至关重要.
- 细胞外囊泡在癌症进展期间调解TGF-β信号传递中的作用仍然不完全理解.
研究的目的:
- 调查小细胞外囊泡 (sEVs) 在调解TGF-β信号和驱动乳腺癌转移中的作用.
- 探索针对sEV分泌以控制癌症进展的治疗潜力.
主要方法:
- 在高度转移的乳腺癌细胞中利用sEV分泌的遗传干扰.
- 评估了对sEV和可溶性TGF-β的反应中的TGF-β信号水平.
- 给药的二甲基胺 (DMA) 在体内抑制sEV分泌.
- 将DMA与SB431542 (TGF-β抑制剂) 结合使用,以评估对转移的协同效应.
主要成果:
- 转移性乳腺癌细胞中的TGF-β信号过活化取决于增加的sEV分泌.
- sEVs诱导的TGF-β信号水平高于同等度的可溶性TGF-β.
- 破坏sEV分泌会降低癌细胞的攻击性和TGF-β信号传递.
- 用DMA抑制sEV分泌会降低体内瘤进展.
- 与DMA和SB431542的联合治疗有力地减少了循环中的瘤细胞和转移.
结论:
- 小细胞外囊泡 (sEVs) 是乳腺癌转移中的TGF-β生物学的关键媒介.
- 针对sEV贩运是一种新的治疗策略,可以使TGF-β信号正常化并抑制转移.
- 抑制sEV分泌可以降低癌细胞的攻击性,减少转移负担.
相关概念视频
Mitogens and the Cell Cycle
6.5K
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...
6.5K
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
TGF - β Signaling Pathway
7.4K
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...
7.4K
Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
Regulation of Angiogenesis and Blood Supply
2.6K
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...
2.6K
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


