ERα/LKB1复合物高调节E-cadherin的表达,并刺激乳腺癌的生长和进展在阿迪波内克暴露后
Giuseppina Daniela Naimo1, Martina Forestiero1, Alessandro Paolì1
1Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
International journal of cancer
|June 16, 2023
概括
阿迪波内克丁通过增加E-cadherin来促进ERα阳性乳腺癌的生长,这会破坏细胞极性并促进转移. 这突出显示了脂肪菌素.
科学领域:
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 脂肪细胞分泌的蛋白质阿迪波涅丁 (Adiponectin) 与肥胖相关的乳腺癌有关.
- 雌激素受体α (ERα) 信号传递对于ERα阳性乳腺癌的扩散至关重要.
- 乙素在细胞粘附,极性和癌症进展方面发挥着作用.
研究的目的:
- 阐明阿迪波涅丁促进ERα阳性乳腺癌生长和转移的机制.
- 研究ERα/LKB1复合体在调节E-cadherin表达中的作用.
- 评估阿迪波内克丁诱导的E-cadherin变化对细胞极性和瘤进展的影响.
主要方法:
- 使用ERα阳性乳腺癌细胞 (MCF-7) 的二维和三维细胞培养物的体外研究.
- 对E-cadherin基因促进活性和蛋白质表达的分析.
- 免疫光显微镜可用于可视化蛋白质定位 (LKB1,Cdc42).
- 在体内研究,包括在小鼠模型中进行正管植入和尾静脉注射.
主要成果:
- 阿迪波涅克丁治疗通过ERα/LKB1复合体介导的促进体激活,增加了ERα阳性乳腺癌细胞中的E-cadherin表达.
- 降低E-cadherin可以消除adiponectin的增殖效应,证实其至关重要的作用.
- 暴露于阿迪波内克导致LKB1和Cdc42的核共定位,破坏了细胞极性.
- 在体内,阿迪波涅丁增强了瘤生长和增加了肺转移.
结论:
- 阿迪波内克丁增强了ERα阳性乳腺癌中E-cadherin的表达,从而促进了扩散.
- 通过改变LKB1和Cdc42的局部化,阿迪波涅破坏了细胞极性.
- 阿迪波内克丁促进乳腺癌生长和远程转移,强调其在癌症进展中的作用.
相关概念视频
Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
PI3K/mTOR/AKT Signaling Pathway
3.7K
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...
3.7K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Structure of Cadherins
3.4K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.3K
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.
2.3K
Adherens Junctions
4.9K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.9K


