Integrins are the adhesion molecules and transmembrane receptors that consist of α and β subunits. After binding to extracellular matrix components, integrins trigger intracellular signaling and regulate a wide spectrum of cellular functions, including cell survival, proliferation, differentiation and migration. Since the pattern of integrins expression is a key determinant of cell behavior in response to microenvironmental cues, deregulation of integrins caused by various mechanisms has been causally linked to cancer development and progression in several solid tumor types. In this review, we discuss the integrin signalosome with a highlight of a few key pro-oncogenic pathways elicited by integrins, and uncover the mutational and transcriptomic landscape of integrin-encoding genes across human cancers. In addition, we focus on the integrin-mediated control of cancer stem cell and tumor stemness in general, such as tumor initiation, epithelial plasticity, organotropic metastasis and drug resistance. With insights into how integrins contribute to the stem-like functions, we now gain better understanding of the integrin signalosome, which will greatly assist novel therapeutic development and more precise clinical decisions.

中文翻译：

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整合素调节实体瘤的干性：一个新兴的治疗靶点

整联蛋白是由α和β亚基组成的粘附分子和跨膜受体。与细胞外基质成分结合后，整合素会触发细胞内信号传导并调节广泛的细胞功能，包括细胞存活、增殖、分化和迁移。由于整联蛋白的表达模式是响应微环境线索的细胞行为的关键决定因素，因此由各种机制引起的整联蛋白的失调与几种实体瘤类型的癌症发展和进展有因果关系。在这篇综述中，我们重点讨论了整合素信号体，重点介绍了整合素引发的一些关键促癌途径，并揭示了人类癌症中整合素编码基因的突变和转录组学景观。此外，我们专注于整合素介导的癌症干细胞和肿瘤干细胞的控制，如肿瘤起始、上皮可塑性、器官转移和耐药性。随着对整合素如何促进干细胞样功能的深入了解，我们现在对整合素信号体有了更好的了解，这将极大地有助于新的治疗开发和更精确的临床决策。