W. Rathmell
Last active: 4/27/2021

Expression of Ror2 mediates invasive phenotypes in renal cell carcinoma.

Rasmussen NR, Debebe Z, Wright TM, Brooks SA, Sendor AB, Brannon AR, Hakimi AA, Hsieh JJ, Choueiri TK, Tamboli P, Maranchie JK, Hinds P, Wallen EM, Simpson C, Norris JL, Janzen WP, Rathmell WK
PLoS One. 2014 9 (12): e116101

PMID: 25542006 · PMCID: PMC4277431 · DOI:10.1371/journal.pone.0116101

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.

MeSH Terms (13)

Animals Carcinoma, Renal Cell Cell Line, Tumor Cell Movement Gene Expression Regulation, Neoplastic Humans Kidney Kidney Neoplasms Mice, Nude Mutation Neoplasm Invasiveness Prognosis Receptor Tyrosine Kinase-like Orphan Receptors

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