Department of Microbiology and Immunology, and Cancer Research Institute, Queen's University, Kingston, ON K7L 3N6.
Biochem Cell Biol. 2009 Dec;87(6):835-43. doi: 10.1139/o09-061.
Cells in normal tissues or in tumors have extensive opportunities for adhesion to their neighbors and the importance of cell to cell contact in the study of fundamental cellular processes is beginning to emerge. In this review, we discuss recent evidence of dramatic changes in the activity of an important signal transducer found to be profoundly affected by cell to cell adhesion, the signal transducer and activator of transcription-3 (Stat3). Direct cadherin engagement, growth of cells to postconfluence, or formation of multicellular aggregates were found to induce a striking increase in the levels of Stat3 activity, Rac1/Cdc42, and members of the IL6 receptor family in different settings. This activation was specific to Stat3, in that the levels of the extracellular signal regulated kinase (Erk1/2), a signal transducer often coordinately activated with Stat3 by a number of growth factors or oncogenes, remained unaffected by cell density. Density-dependent Stat3 activation may play a key role in survival, and could contribute to the establishment of cell polarity. It is clear that at any given time the total Stat3 activity levels in a cell are the sum of the effects of cell to cell adhesion plus the conventional Stat3 activating factors present.
正常组织或肿瘤中的细胞有广泛的机会与其相邻细胞黏附，细胞间接触在研究基本细胞过程中的重要性开始显现。在这篇综述中，我们讨论了最近的证据，表明一种重要信号转导物的活性发生了显著变化，这种信号转导物和转录激活因子 3（Stat3）被发现受到细胞间黏附的深刻影响。在不同的环境中，直接黏附连接蛋白、细胞达到汇合后生长或形成多细胞聚集体，被发现会显著增加 Stat3 活性、Rac1/Cdc42 和白细胞介素 6 受体家族成员的水平。这种激活是 Stat3 特有的，因为细胞密度对细胞外信号调节激酶（Erk1/2）的水平没有影响，Erk1/2 是一种信号转导物，通常通过许多生长因子或癌基因与 Stat3 协同激活。密度依赖的 Stat3 激活可能在生存中发挥关键作用，并有助于建立细胞极性。很明显，在任何给定的时间，细胞中总 Stat3 活性水平是细胞间黏附的影响加上存在的传统 Stat3 激活因子的总和。
