Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology.
Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology.
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DOI：
10.1111/bph.13894
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发表时间：
2017-12
影响因子：
7.3
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Kagey MH;He X
Wnt信号转导是胚胎发育和成体组织稳态的基本途径。该途径的突变经常导致发育缺陷和癌症。因此，对该途径的治疗干预引起了极大的兴趣。Dickkopf-1（DKK 1）是β-catenin-依赖性Wnt信号传导的分泌型抑制剂，最初被描述为肿瘤抑制剂，基于Wnt信号传导促进癌症发病机制的流行观点。然而，DKK 1似乎增加了临床前模型中的肿瘤生长和转移，并且其升高的表达与一系列癌症的不良预后相关，表明DKK 1具有比最初认识到的更复杂的细胞和生物学功能。在这里，我们回顾了DKK 1促癌活性的现有证据，以及DKK 1对癌症和免疫细胞信号通路影响的最新见解。我们讨论了靶向DKK 1用于肿瘤学的基本原理和前景。这篇文章是WNT信号传导的主题部分的一部分：机制和治疗机会。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
Wnt signalling is a fundamental pathway involved in embryonic development and adult tissue homeostasis. Mutations in the pathway frequently lead to developmental defects and cancer. As such, therapeutic intervention of this pathway has generated tremendous interest. Dickkopf‐1 (DKK1) is a secreted inhibitor of β‐catenin‐dependent Wnt signalling and was originally characterized as a tumour suppressor based on the prevailing view that Wnt signalling promotes cancer pathogenesis. However, DKK1 appears to increase tumour growth and metastasis in preclinical models and its elevated expression correlates with a poor prognosis in a range of cancers, indicating that DKK1 has more complex cellular and biological functions than originally appreciated. Here, we review current evidence for the cancer‐promoting activity of DKK1 and recent insights into the effects of DKK1 on signalling pathways in both cancer and immune cells. We discuss the rationale and promise of targeting DKK1 for oncology. This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
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影响因子：
37.3
作者：
Chen L;Li M;Li Q;Wang CJ;Xie SQ
通讯作者：
Xie SQ
影响因子：
11.8
作者：
Chen, Shuo;Bubeck, Doryen;MacDonald, Bryan T.;Liang, Wen-Xue;Mao, Jian-Hua;Malinauskas, Tomas;Llorca, Oscar;Aricescu, A. Radu;Siebold, Christian;He, Xi;Jones, E. Yvonne
通讯作者：
Jones, E. Yvonne
影响因子：
--
作者：
Aguilera Ó;González-Sancho JM;Zazo S;Rincón R;Fernández AF;Tapia O;Canals F;Morte B;Calvanese V;Orgaz JL;Niell N;Aguilar S;Freije JM;Graña O;Pisano DG;Borrero A;Martínez-Useros J;Jiménez B;Fraga MF;García-Foncillas J;López-Otín C;Lafarga M;Rojo F;Muñoz A
通讯作者：
Muñoz A
DOI：
10.1084/jem.20150950
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
D'Amico L;Mahajan S;Capietto AH;Yang Z;Zamani A;Ricci B;Bumpass DB;Meyer M;Su X;Wang-Gillam A;Weilbaecher K;Stewart SA;DeNardo DG;Faccio R
通讯作者：
Faccio R
影响因子：
6.4
作者：
Bu, Guojun;Lu, Wenyan;Liu, Chia-Chen;Selander, Katri;Yoneda, Toshiyuki;Hall, Christopher;Keller, Evan T.;Li, Yonghe
通讯作者：
Li, Yonghe