英國一項最新研究發(fā)現(xiàn)一個促使癌細(xì)胞擴(kuò)散的“幫兇”基因，如果用藥物抑制這個基因的作用,，癌細(xì)胞將不易擴(kuò)散,。研究人員稱，這一發(fā)現(xiàn)將有助于提高癌癥治療水平,。
英國東英吉利大學(xué)研究人員在新一期《致癌基因》（Oncogene）雜志上報告說,，通常在某部位組織出現(xiàn)癌變后，人體內(nèi)會有一種天然物質(zhì)來控制癌細(xì)胞不讓其擴(kuò)散,，但名為WWP2的基因會減弱這種天然物質(zhì)的功效,，幫助癌細(xì)胞擴(kuò)散。研究人員在試管試驗中發(fā)現(xiàn),，如果用藥物抑制這一基因的作用,，癌細(xì)胞可被有效控制在原發(fā)部位。
領(lǐng)導(dǎo)研究的安德魯·錢特里說,，在癌癥后期,，癌細(xì)胞會大量轉(zhuǎn)移擴(kuò)散到身體其他部位，這種擴(kuò)散是最難控制的,。如果能將癌細(xì)胞控制在原發(fā)部位,，將可使手術(shù)介入等治療更加有效。
他說,，接下來的工作是在本次研究基礎(chǔ)上開發(fā)出可用于臨床治療的藥物,，這種藥物也許能在10年內(nèi)問世。這將是新一代抗癌藥物,。（生物谷Bioon.com）
生物谷推薦原文出處：
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
