Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
J Cell Sci. 2011 Oct 1;124(Pt 19):3189-97. doi: 10.1242/jcs.072165.
Anoikis (or cell-detachment-induced apoptosis) is a self-defense strategy that organisms use to eliminate 'misplaced' cells, i.e. cells that are in an inappropriate location. Occasionally, detached or misplaced cells can overcome anoikis and survive for a certain period of time in the absence of the correct signals from the extracellular matrix (ECM). If cells are able to adapt to their new environment, then they have probably become anchorage-independent, which is one of the hallmarks of cancer cells. Anoikis resistance and anchorage-independency allow tumor cells to expand and invade adjacent tissues, and to disseminate through the body, giving rise to metastasis. Thus, overcoming anoikis is a crucial step in a series of changes that a tumor cell undergoes during malignant transformation. Tumor cells have developed a variety of strategies to bypass or overcome anoikis. Some strategies consist of adaptive cellular changes that allow the cells to behave as they would in the correct environment, so that induction of anoikis is aborted. Other strategies aim to counteract the negative effects of anoikis induction by hyperactivating survival and proliferative cascades. The recently discovered processes of autophagy and entosis also highlight the contribution of these mechanisms to rendering the cells in a dormant state until they receive a signal initiated at the ECM, thereby circumventing anoikis. In all situations, the final outcome is the ability of the tumor to grow and metastasize. A better understanding of the mechanisms underlying anoikis resistance could help to counteract tumor progression and prevent metastasis formation.
细胞失巢凋亡（或细胞脱离诱导的细胞凋亡）是一种生物体用来消除“错位”细胞（即在不合适位置的细胞）的自我防御策略。偶尔，分离或错位的细胞可以克服细胞失巢凋亡，并在缺乏细胞外基质（ECM）的正确信号的情况下存活一段时间。如果细胞能够适应新的环境，那么它们可能已经变得不依赖于锚定，这是癌细胞的标志之一。抗细胞失巢凋亡和不依赖锚定使肿瘤细胞能够扩张并侵袭相邻组织，并通过身体传播，导致转移。因此，克服细胞失巢凋亡是肿瘤细胞在恶性转化过程中经历的一系列变化中的关键步骤。肿瘤细胞已经开发出多种策略来绕过或克服细胞失巢凋亡。一些策略包括适应性细胞变化，使细胞能够像在正确环境中那样行为，从而中止细胞失巢凋亡的诱导。其他策略旨在通过过度激活生存和增殖级联来抵消细胞失巢凋亡诱导的负面影响。最近发现的自噬和侵入过程也强调了这些机制对使细胞处于休眠状态的贡献，直到它们接收到 ECM 发起的信号，从而绕过细胞失巢凋亡。在所有情况下，最终结果是肿瘤的生长和转移能力。更好地了解抗细胞失巢凋亡的机制可能有助于对抗肿瘤进展并防止转移形成。
