title: 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.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Neal R
authors.initials: NR
authors.lastname: Rasmussen
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Zufan
authors.initials: Z
authors.lastname: Debebe
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Tricia M
authors.initials: TM
authors.lastname: Wright
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Samira A
authors.initials: SA
authors.lastname: Brooks
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Sendor
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: A Rose
authors.initials: AR
authors.lastname: Brannon
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America; Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America; Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: Department of Medical Oncology and Kidney Cancer Center, Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States of America.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, Houston, Texas, 77030, United States of America.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Department of Urologic Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15219, United States of America.
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Maranchie
authors.affiliation: Department of Urologic Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15219, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Hinds
authors.affiliation: Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wallen
authors.affiliation: Center for Integrative Chemical Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Simpson
authors.affiliation: Center for Integrative Chemical Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Norris
authors.affiliation: Center for Integrative Chemical Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: William P
authors.initials: WP
authors.lastname: Janzen
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America; Departments of Medicine and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000032:analysis / Q000235:genetics*
chemical_list: C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors