Medical School of Fudan University, Shanghai, China.
Cancer Lett. 2013 Aug 19;336(2):290-8. doi: 10.1016/j.canlet.2013.03.014. Epub 2013 Mar 21.
Transforming growth factor activated kinase 1 (TAK1) provides prosurvival signals in various types of cells, and emerging evidence indicates that targeting TAK1 is a promising means to eliminate certain types of cancer cells. Here, we show that TAK1 is required for efficient tumorigenicity of AKT-transformed cells. TAK1 inhibition accelerates cell apoptosis of AKT-transformed cells in anchorage-independent cell growth accompanying by the downregulation of Mcl-1 and Bcl-2 expression. On the contrary, the tumorigenicity of c-Myc-transformed cells is not significantly affected by TAK1 inhibition. Moreover, AKT-transformed cells with c-Myc overexpression tolerate TAK1 inhibition in anchorage-independent growth and tumorigenicity in vivo. Together, our results provide evidence that TAK1-dependency in the tumorigenicity of AKT-transformed cells can be alleviated by c-Myc overexpression. These findings suggest that dual-targeting TAK1 and c-Myc might be a rational therapeutic strategy for treatment of certain types of cancer.
转化生长因子激活激酶 1（TAK1）在各种类型的细胞中提供生存信号，新出现的证据表明，靶向 TAK1 是消除某些类型癌细胞的有前途的手段。在这里，我们表明 TAK1 是 AKT 转化细胞有效致瘤所必需的。TAK1 抑制加速 AKT 转化细胞在无锚定细胞生长中的细胞凋亡，同时下调 Mcl-1 和 Bcl-2 的表达。相反，c-Myc 转化细胞的致瘤性不受 TAK1 抑制的显著影响。此外，c-Myc 过表达的 AKT 转化细胞在无锚定生长和体内致瘤性中耐受 TAK1 抑制。总之，我们的结果提供了证据，表明 TAK1 在 AKT 转化细胞致瘤性中的依赖性可以通过 c-Myc 过表达来缓解。这些发现表明，双重靶向 TAK1 和 c-Myc 可能是治疗某些类型癌症的合理治疗策略。
