Smad ubiquitination regulatory factor 1 (Smurf1) and Smurf2 are HECT-type E3 ubiquitin ligases, and both Smurfs were initially identified to regulate Smad protein stability in the TGF-β/BMP signaling pathway. In recent years, Smurfs have exhibited E3 ligase-dependent and -independent activities in various kinds of cells. Smurfs act as either potent tumor promoters or tumor suppressors in different tumors by regulating biological processes, including metastasis, apoptosis, cell cycle, senescence and genomic stability. The regulation of Smurfs activity and expression has therefore emerged as a hot spot in tumor biology research. Further, the Smurf1- or Smurf2-deficient mice provide more in vivo clues for the functional study of Smurfs in tumorigenesis and development. In this review, we summarize these milestone findings and, in turn, reveal new avenues for the prevention and treatment of cancer by regulating Smurfs.

Smad 泛素化调节因子 1 (Smurf1) 和 Smurf2 是 HECT 型 E3 泛素连接酶，这两种 Smurf 最初被鉴定为调节 TGF-β/BMP 信号通路中 Smad 蛋白的稳定性。近年来，蓝精灵在各种细胞中都表现出依赖 E3 连接酶和不依赖 E3 连接酶的活性。Smurfs 通过调节生物过程，包括转移、细胞凋亡、细胞周期、衰老和基因组稳定性，在不同的肿瘤中充当有效的肿瘤促进剂或抑癌剂。因此，Smurfs 活性和表达的调控已成为肿瘤生物学研究的热点。此外，Smurf1或Smurf2缺陷小鼠提供更多的体内蓝精灵在肿瘤发生和发展中的功能研究的线索。在这篇综述中，我们总结了这些里程碑式的发现，进而揭示了通过调节 Smurfs 来预防和治疗癌症的新途径。