Expression of Ror2 mediates invasive phenotypes in renal cell carcinoma.

Abstract	Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer.
Authors	Neal R Rasmussen, Zufan Debebe, Tricia M Wright, Samira A Brooks, Adam B Sendor, A Rose Brannon, A Ari Hakimi, James J Hsieh, Toni K Choueiri, Pheroze Tamboli, Jodi K Maranchie, Peter Hinds, Eric M Wallen, Catherine Simpson, Jacqueline L Norris, William P Janzen, W Kimryn Rathmell
Journal	PloS one (PLoS One) Vol. 9 Issue 12 Pg. e116101 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID	25542006 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	ROR2 protein, human Receptor Tyrosine Kinase-like Orphan Receptors
Topics	Animals Carcinoma, Renal Cell (diagnosis, genetics, pathology) Cell Line, Tumor Cell Movement Gene Expression Regulation, Neoplastic Humans Kidney (metabolism, pathology) Kidney Neoplasms (diagnosis, genetics, pathology) Mice, Nude Mutation Neoplasm Invasiveness (diagnosis, genetics, pathology) Prognosis Receptor Tyrosine Kinase-like Orphan Receptors (analysis, genetics)

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