矩阵交叉连接通过增强整合素信号传递来强化瘤的进展
Kandice R Levental1, Hongmei Yu, Laura Kass
1Department of Bioengineering and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|November 26, 2009
概括
由原交叉连接驱动的瘤硬性通过增加焦点粘附和PI3激酶活性促进癌症. 减少这种交叉连接阻碍恶性瘤,降低乳腺癌中的瘤发病率.
科学领域:
- 在瘤学瘤学.
- 生物化学 生物化学
- 生物物理学的生物物理.
背景情况:
- 瘤表现出细胞外基质 (ECM) 改造和硬化,但硬化在癌症进展中的作用尚未完全理解.
- 虽然在癌症中已认识到ECM重塑,但ECM硬化对瘤发生的具体贡献需要进一步阐明.
研究的目的:
- 调查原交叉连接和ECM硬化在乳腺癌进展中的作用.
- 为了确定ECM刚性,焦点粘附,PI3激酶信号传递和乳腺恶性瘤之间的机械联系.
主要方法:
- 使用lysyl氧化酶诱导和抑制原蛋白交联.
- 评估ECM刚度,焦点粘附和PI3激酶 (PI3K) 活性.
- 使用MMTV-Neu小鼠模型进行体内研究,以评估瘤发病率和纤维化.
主要成果:
- 原交叉连接导致ECM硬化,增加焦点粘附,增强PI3K活性,并促进上皮细胞入侵.
- 抑制整合素信号减少了对硬化的ECM的入侵,而整合素聚类促进了焦点粘附和PI3K信号.
- 降低 lysyl氧化酶介导的原交叉连接可以预防纤维化,减少焦点粘附和PI3K活性,并阻碍乳腺恶性瘤.
结论:
- 原交叉连接是乳腺瘤发生过程中ECM硬化和纤维化的关键驱动因素.
- 通过原交联介导的ECM硬化促进焦点粘附和PI3K信号传递,从而推动乳腺癌的进展.
- 向lysyl氧化酶介导的原交叉连接代表了阻止乳腺恶性瘤的潜在治疗策略.
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