β4整合素增强ErbB2信号传递,促进乳腺瘤发生
Wenjun Guo1, Yuliya Pylayeva, Angela Pepe
1Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 USA.
Cell
|August 12, 2006
概括
β4整合素增强了ErbB2信号传输,促进了侵袭性乳腺癌. 向β4信号抑制瘤生长,增强ErbB2向治疗的疗效.
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:
- 在侵袭性乳腺瘤中,ErbB2基因的放大是常见的,与预后不佳有关.
- ErbB2驱动的乳腺癌进展机制尚未完全理解.
- β4整合素是一种细胞粘附和信号受体,与瘤发生有关.
研究的目的:
- 调查β4整合素信号传导在ErbB2介导乳腺癌中的作用.
- 确定β4整合素是否有助于瘤发病,入侵和治疗反应.
主要方法:
- 利用了ErbB2诱导的乳腺癌的小鼠模型.
- 引入了针对β4整合蛋白信号域的有针对性的删除.
- 进行了ex vivo研究,分析蛋白质复合体的形成和转录因子的激活.
主要成果:
- 失去了β4整合素信号,抑制了乳腺瘤的发病和侵入性生长.
- β4整合素与ErbB2形成复合体,增强STAT3和c-Jun的激活.
- 观察到STAT3上皮质粘附/极性和c-Jun驱动的过度扩散的破坏.
- 删除β4信号域改善了ErbB2向治疗的疗效.
结论:
- β4整合素通过放大ErbB2信号通路来促进乳腺癌的进展.
- β4整合素被确定为乳腺癌的潜在治疗标.
- 向β4整合素可能会增强现有的ErbB2向疗法.
相关概念视频
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...
mTOR Signaling and Cancer Progression
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...
PI3K/mTOR/AKT Signaling Pathway
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 rapamycin-insensitive companion...
TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Affects Focal Adhesions
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...
Some...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
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.


