Department of Translational Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
Department of Cancer Biology and David H. Koch Center for Applied Research of Genitourinary Cancers, UT MD Anderson Cancer Center, Houston, TX 77054, USA.
Cancer Cell. 2019 Mar 18;35(3):347-367. doi: 10.1016/j.ccell.2019.01.007.
Integrins mediate cell adhesion and transmit mechanical and chemical signals to the cell interior. Various mechanisms deregulate integrin signaling in cancer, empowering tumor cells with the ability to proliferate without restraint, to invade through tissue boundaries, and to survive in foreign microenvironments. Recent studies have revealed that integrin signaling drives multiple stem cell functions, including tumor initiation, epithelial plasticity, metastatic reactivation, and resistance to oncogene- and immune-targeted therapies. Here, we discuss the mechanisms leading to the deregulation of integrin signaling in cancer and its various consequences. We place emphasis on novel functions, determinants of context dependency, and mechanism-based therapeutic opportunities.
整合素介导细胞黏附，并将机械和化学信号传递到细胞内部。在癌症中，各种机制会使整合素信号失调，使肿瘤细胞能够不受限制地增殖、穿透组织边界侵袭、并在异质微环境中存活。最近的研究表明，整合素信号驱动多种干细胞功能，包括肿瘤起始、上皮可塑性、转移再激活以及对致癌基因和免疫靶向治疗的耐药性。在这里，我们讨论导致癌症中整合素信号失调的机制及其各种后果。我们强调新的功能、上下文依赖性的决定因素和基于机制的治疗机会。
