Overcoming anoikis - pathways to anchorage-independent growth in cancer
Overcoming anoikis - pathways to anchorage-independent growth in cancer
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DOI：
10.1242/jcs.072165
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
del Pozo, Miguel A.
中科院分区：
文献类型：
--
作者：
Guadamillas, Marta C.;Cerezo, Ana;del Pozo, Miguel A.
失巢凋亡（Anoikis）是生物体用来消除“错位”细胞（即处于不适当位置的细胞）的一种自我防御策略。有时，脱落或错位的细胞可以克服失巢凋亡，并在缺乏来自细胞外基质（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。失巢凋亡抗性和锚定独立性允许肿瘤细胞扩张并侵入邻近组织，并通过身体扩散，引起转移。因此，克服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一步。肿瘤细胞已经开发了各种策略来绕过或克服失巢凋亡。一些策略包括适应性细胞变化，允许细胞表现得像它们在正确的环境中一样，从而中止失巢凋亡的诱导。其他策略旨在通过过度激活存活和增殖级联反应来抵消失巢凋亡诱导的负面影响。最近发现的自噬和内吞过程也突出了这些机制的贡献，使细胞处于休眠状态，直到它们接收到ECM发出的信号，从而避免失巢凋亡。在所有情况下，最终结果是肿瘤生长和转移的能力。更好地了解失巢凋亡抵抗的机制有助于对抗肿瘤进展和防止转移形成。
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.