Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Sci Signal. 2012 Apr 10;5(219):pe15. doi: 10.1126/scisignal.2002921.
Two papers published in Science Signaling reveal extensive crosstalk between Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling in cancer. Although both studies describe previously unknown links between these two signaling pathways, the relationship between Wnt/β-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/β-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/β-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/β-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/β-catenin signaling may have anti-oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/β-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/β-catenin pathway for all cancers.
两篇发表在《科学信号》上的论文揭示了癌症中 Wnt/β-连环蛋白和丝裂原活化蛋白激酶 (MAPK) 信号之间广泛的串扰。尽管这两项研究都描述了这两种信号通路之间以前未知的联系，但 Wnt/β-连环蛋白和 MAPK 信号之间的关系取决于特定的细胞环境。事实上，在黑色素瘤中，过度活跃的 MAPK 信号会下调 Wnt/β-连环蛋白信号转导级联，从而在这两个信号通路之间建立负性串扰。相比之下，在结直肠癌中，Wnt/β-连环蛋白途径的刺激通过 Ras 稳定导致 MAPK 途径的激活，代表了正性串扰的一个例子。此外，Wnt/β-连环蛋白信号的激活具有与上下文相关的功能，对肿瘤生长产生相反的影响。在黑色素瘤中，Wnt/β-连环蛋白信号的异常激活可能通过促进程序性细胞死亡具有抗肿瘤功能；相比之下，在肠道中，Wnt/β-连环蛋白信号驱动恶性转化。因此，针对所有癌症，靶向 Wnt/β-连环蛋白途径没有单一正确的方法。
