The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma.
The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma.
复制标题
DOI：
10.1038/onc.2009.305
复制
发表时间：
2010-01-07
期刊：
影响因子：
8
通讯作者：
Weeraratna, A. T.
中科院分区：
文献类型：
--
作者：
O'Connell, M. P.;Fiori, J. L.;Xu, M.;Carter, A. D.;Frank, B. P.;Camilli, T. C.;French, A. D.;Dissanayake, S. K.;Indig, F. E.;Bernier, M.;Taub, D. D.;Hewitt, S. M.;Weeraratna, A. T.
Tyrosine kinase receptors represent targets of great interest for cancer therapy. Here we demonstrate, for the first time, the importance of the orphan tyrosine kinase receptor, ROR2, in melanoma progression. Using melanoma tissue microarrays we show that ROR2 is expressed predominantly in metastatic melanoma. Because ROR2 has been shown to specifically interact with the non-canonical Wnt ligand, Wnt5A, this corroborates our previous data implicating Wnt5A as a mediator of melanoma metastasis. We show here that increases in Wnt5A cause increases in ROR2 expression, as well as the PKC-dependent, clathrin-mediated internalization of ROR2. WNT5A knockdown by siRNA decreases ROR2 expression, but silencing of ROR2 has no effect on WNT5A levels. ROR2 knockdown does, however, result in a decrease in signaling downstream of Wnt5A. Using in vitro and in vivo metastasis assays we demonstrate that ROR2 is necessary for the Wnt5A-mediated metastasis of melanoma cells. These data imply that ROR2 may represent a novel target for melanoma therapy.
登录
查看更多内容
DOI：
10.1038/jid.2008.433
发表时间：
2009-07
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
O'Connell MP;Fiori JL;Baugher KM;Indig FE;French AD;Camilli TC;Frank BP;Earley R;Hoek KS;Hasskamp JH;Elias EG;Taub DD;Bernier M;Weeraratna AT
通讯作者：
Weeraratna AT
影响因子：
11.5
作者：
Safholm, Annette;Tuomela, Johanna;Andersson, Tommy
通讯作者：
Andersson, Tommy
影响因子：
2.1
作者：
Oishi, I;Suzuki, H;Minami, Y
通讯作者：
Minami, Y
影响因子：
16.2
作者：
Howe, CL;Valletta, JS;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
30.8
作者：
Oldridge, M;Fortuna, AM;Wilkie, AOM
通讯作者：
Wilkie, AOM