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Integrating integrins with the hallmarks of cancer
Matrix Biology ( IF 6.9 ) Pub Date : 2024-04-25 , DOI: 10.1016/j.matbio.2024.04.003
Scott M. Haake , Brenda L. Rios , Ambra Pozzi , Roy Zent

Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the “Hallmarks of Cancer” from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics.

中文翻译:


将整合素与癌症特征相结合



上皮细胞粘附在一种称为基底膜的特殊细胞外基质上,使它们能够极化并形成上皮组织。细胞外基质提供组织形态发生、分化、功能和稳态所需的重要物理支架以及生化和生物物理线索。上皮细胞与细胞外基质(即基底膜)的粘附在组织上皮组织、将上皮细胞与基质分离方面起着关键作用。上皮细胞从基底膜脱离通常会导致死亡,尽管通过基底膜的脱离或侵袭代表着癌发生的关键步骤。上皮细胞通过特殊的基质受体(包括整合素)与细胞外基质结合。整合素是跨膜受体,在细胞外基质和细胞内细胞骨架之间形成机械连接,并且是锚定依赖性细胞功能(例如增殖、迁移和侵袭)所必需的。整合素在多种癌症的发生、生长和传播中的作用已经通过多种方法进行了研究,这导致了极大的复杂性。为了整理大量信息,我们利用 Hanahan 和 Weinberg 的“癌症标志”作为讨论整合素在癌症发病机制中的作用的便捷框架。这篇综述探讨了这种生物学及其复杂性如何影响整合素靶向抗癌疗法的发展。
更新日期:2024-04-25
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