Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
Cancers (Basel). 2014 Jul 3;6(3):1408-40. doi: 10.3390/cancers6031408.
The roles and significance of STAT3 in cancer biology have been extensively studied for more than a decade. Mounting evidence has shown that constitutive activation of STAT3 is a frequent biochemical aberrancy in cancer cells, and this abnormality directly contributes to tumorigenesis and shapes many malignant phenotypes in cancer cells. Nevertheless, results from more recent experimental and clinicopathologic studies have suggested that STAT3 also can exert tumor suppressor effects under specific conditions. Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. Thus, in the context of cancer biology, STAT3 can be a friend or foe. In the first half of this review, we will highlight the "evil" features of STAT3 by summarizing its oncogenic functions and mechanisms. The differences between the canonical and non-canonical pathway will be highlighted. In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. To explain how STAT3 may mediate its tumor suppressor effects, we will discuss several possible mechanisms, one of which is linked to the role of STAT3β, one of the two STAT3 splicing isoforms. Taken together, it is clear that the roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously. The new knowledge has provided us with new approaches and strategies when we evaluate STAT3 as a prognostic biomarker or therapeutic target.
STAT3 在癌症生物学中的作用和意义已经被研究了十余年。越来越多的证据表明，STAT3 的组成性激活是癌细胞中常见的生化异常，这种异常直接导致肿瘤发生，并塑造了癌细胞中的许多恶性表型。然而，最近的实验和临床病理研究结果表明，STAT3 在特定条件下也可以发挥肿瘤抑制作用。重要的是，其中一些研究表明，STAT3 可以在同一细胞类型中作为癌蛋白或肿瘤抑制因子发挥作用，这取决于特定的遗传背景或是否存在特定的共存生化缺陷。因此，在癌症生物学中，STAT3 可以是朋友，也可以是敌人。在这篇综述的前半部分，我们将通过总结其致癌功能和机制来强调 STAT3 的“邪恶”特征。我们将重点介绍经典途径和非经典途径之间的差异。在后半部分，我们将总结支持 STAT3 可以作为肿瘤抑制因子发挥作用的证据。为了解释 STAT3 如何介导其肿瘤抑制作用，我们将讨论几种可能的机制，其中之一与 STAT3 剪接异构体之一 STAT3β 的作用有关。总之，STAT3 在癌症中的作用是多方面的，远比以前人们所理解的要复杂得多。这些新知识为我们评估 STAT3 作为预后生物标志物或治疗靶点提供了新的方法和策略。
