Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma.
Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma.
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DOI：
10.1038/onc.2009.116
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发表时间：
2009-07-09
期刊：
影响因子：
8
通讯作者：
Rathmell, W. K.
中科院分区：
文献类型：
--
作者：
Wright, T. M.;Brannon, A. R.;Gordan, J. D.;Mikels, A. J.;Mitchell, C.;Chen, S.;Espinosa, I.;van de Rijn, M.;Pruthi, R.;Wallen, E.;Edwards, L.;Nusse, R.;Rathmell, W. K.
激酶不适当的表达和随后的混杂活性决定了包括肾细胞癌（RCC）在内的许多实体瘤的转化。因此，新型肿瘤相关激酶的表达具有显著影响肿瘤细胞行为的潜力。此外，鉴定肿瘤相关激酶可以帮助我们深入了解肿瘤的生长模式和特征。在这里，我们报道了在RCC细胞系和原发肿瘤中发现的Ror2，一种新的肿瘤相关激酶。Ror2是一种孤儿受体酪氨酸激酶，其生理表达通常见于胚胎肾。然而，在RCC中，Ror2的表达与细胞外基质相关基因的表达相关，包括Twist和基质金属蛋白酶2 （MMP2）。Ror2敲低可抑制RCC细胞中MMP2的表达，这表明Ror2是RCC中MMP2调控的中介，也是细胞外基质重塑的潜在调节剂。Ror2的抑制不仅抑制了细胞的迁移，还抑制了软琼脂中锚定独立生长和原位异种移植模型的生长。这些发现提示了Ror2在肾癌亚群中促进肿瘤活性的新途径，对揭示RCC的肿瘤发生具有重要意义。
Inappropriate kinase expression and subsequent promiscuous activity defines the transformation of many solid tumors including renal cell carcinoma (RCC). Thus, the expression of novel tumor-associated kinases has the potential to dramatically shape tumor cell behavior. Further, identifying tumor-associated kinases can lend insight into patterns of tumor growth and characteristics. Here, we report the identification of Ror2, a new tumor-associated kinase in RCC cell lines and primary tumors. Ror2 is an orphan receptor tyrosine kinase with physiological expression normally seen in the embryonic kidney. However, in RCC, Ror2 expression correlated with expression of genes involved at the extracellular matrix, including Twist and matrix metalloprotease-2 (MMP2). Expression of MMP2 in RCC cells was suppressed by Ror2 knockdown, placing Ror2 as a mediator of MMP2 regulation in RCC and a potential regulator of extracellular matrix remodeling. The suppression of Ror2 not only inhibited cell migration, but also inhibited anchorage independent growth in soft agar and growth in an orthotopic xenograft model. These findings suggest a novel pathway of tumor-promoting activity by Ror2 within a subset of renal carcinomas, with significant implications for unraveling the tumorigenesis of RCC.
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DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
DOI：
10.1016/s0022-2143(97)90180-3
发表时间：
1997-03-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Racusen, LC;Monteil, C;Morin, JP
通讯作者：
Morin, JP
影响因子：
45.3
作者：
Atkins, MB;Hidalgo, M;Sherman, ML
通讯作者：
Sherman, ML
影响因子：
3.4
作者：
de Castro-Carpeno, Javier;Belda-Iniesta, Cristobal;Gonzalez Baron, Manuel
通讯作者：
Gonzalez Baron, Manuel
影响因子：
30.8
作者：
Oldridge, M;Fortuna, AM;Wilkie, AOM
通讯作者：
Wilkie, AOM