Integrins, oncogenes, and anchorage independence.
Integrins, oncogenes, and anchorage independence.
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DOI：
10.1083/jcb.139.3.575
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发表时间：
1997-11-03
期刊：
影响因子：
--
通讯作者：
Schwartz MA
中科院分区：
文献类型：
--
作者：
Schwartz MA
癌细胞在没有细胞外基质（ECM）1蛋白粘附的情况下增殖的能力（称为生长的锚定独立性）与动物模型中的致瘤性密切相关（14）。癌细胞的这种特性可能反映了肿瘤细胞在体内不适当的位置存活和生长的趋势。这种不正确的定位，如发生在浸润和转移，是恶性肿瘤与良性肿瘤的区别特征（31）。在过去的20年里，人们在理解正常细胞的生长是如何被控制的以及癌基因是如何篡夺这些控制的方面取得了巨大的进展。然而，关于癌基因（或肿瘤抑制因子的缺失）如何克服控制细胞定位的机制的研究却相当滞后。整合素介导影响细胞内生长调节途径的信号的发现为锚定依赖性提供了一些见解。现有的证据表明，整合素依赖的信号介导细胞粘附到ECM蛋白的生长需要。我们对整合素信号的理解现在已经达到了一个阶段，与肿瘤发生的联系越来越清楚，使我们能够将一些原癌基因和癌基因与它们的粘附依赖性或独立性。虽然许多分子机制的细节仍有待阐明，但现在已有足够的信息来提出一个关于癌基因如何导致锚定非依赖性生长的总体框架。
The ability of cancer cells to proliferate in the ab-sence of adhesion to extracellular matrix (ECM) 1 proteins, termed anchorage independence of growth, correlates closely with tumorigenicity in animal models (14). This property of cancer cells presumably reflects the tendency of tumor cells to survive and grow in inappropriate locations in vivo. Such incorrect localization, as occurs in invasion and metastasis, is the characteristic that distinguishes malignant from benign tumors (31). Great progress has been made in the last 20 years toward understanding how growth is controlled in normal cells and how oncogenes usurp these controls. Yet studies on how oncogenes (or loss of tumor suppressors) overcome the mechanisms that govern cellular location have lagged considerably. The finding that integrins transduce signals that influence intracellular growth regulatory pathways provided some insight into anchorage dependence. Available evidence indicates that integrin-dependent signals mediate the growth requirement for cell adhesion to ECM proteins.Our understanding of integrin signaling has now reached a stage that connections to oncogenesis are becoming clear, enabling us to place a number of proto-oncogenes and oncogenes with respect to their adhesion dependence or independence. While many details of molecular mechanisms remain to be elucidated, sufficient information is now available to propose a general framework for how oncogenes lead to anchorage-independent growth.