英国一项最新研究发现一个促使癌细胞扩散的“帮凶”基因，如果用药物抑制这个基因的作用，癌细胞将不易扩散。研究人员称，这一发现将有助于提高癌症治疗水平。
英国东英吉利大学研究人员在新一期《致癌基因》（Oncogene）杂志上报告说，通常在某部位组织出现癌变后，人体内会有一种天然物质来控制癌细胞不让其扩散，但名为WWP2的基因会减弱这种天然物质的功效，帮助癌细胞扩散。研究人员在试管试验中发现，如果用药物抑制这一基因的作用，癌细胞可被有效控制在原发部位。
领导研究的安德鲁·钱特里说，在癌症后期，癌细胞会大量转移扩散到身体其他部位，这种扩散是最难控制的。如果能将癌细胞控制在原发部位，将可使手术介入等治疗更加有效。
他说，接下来的工作是在本次研究基础上开发出可用于临床治疗的药物，这种药物也许能在10年内问世。这将是新一代抗癌药物。（生物谷Bioon.com）
生物谷推荐原文出处：
Oncogene advance online publication 24 January 2011; doi: 10.1038/onc.2010.617
Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT
S M Soond1 and A Chantry1
Abstract
Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFβ-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFβ pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFβ-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFβ-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFβ-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFβ stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads.
Keywords: TGFβ; Smads; transcription; Ubiquitin ligase
