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Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma

Oncogene volume 28, pages 2513–2523 (2009)Cite this article

Abstract

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 the RTK-like orphan receptor 2 (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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Acknowledgements

We thank the Rathmell Lab members and the Lineberger Cancer Center community for thoughtful insights/advice. Additional thanks to the Microscopy Services Laboratory for use of their facilities, the Lineberger Animal Core Studies Facility and the Baldwin Lab for use of reagents. We also thank Dr H Shelton Earp, Dr Ian Davis and Dr Jon Serody for paper critiques. Funding for this project was provided in part by the Doris Duke Charitable Fund and the V foundation (WKR), Initiative for Maximizing Student Diversity Training Grant NIH-R25GM055336 (TMW and CM) and NCI-F31CA132543 (TMW). Funding for JDG was provided by a MSTP grant and a T32 grant in hemostasis and thrombosis. Human tumor samples were collected by the UNC Tumor Procurement Facility, supported by the UNC Lineberger Comprehensive Cancer Center.

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Authors and Affiliations

  1. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    T M Wright, A R Brannon & W K Rathmell

  2. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    T M Wright, A R Brannon, S Chen, R Pruthi, E Wallen & W K Rathmell

  3. Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA

    J D Gordan

  4. Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA

    A J Mikels & R Nusse

  5. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA

    A J Mikels & R Nusse

  6. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    C Mitchell & L Edwards

  7. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    I Espinosa & M van de Rijn

  8. Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    R Pruthi & E Wallen

  9. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    W K Rathmell

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  1. T M Wright
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Correspondence to W K Rathmell.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Wright, T., Brannon, A., Gordan, J. et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene 28, 2513–2523 (2009). https://doi.org/10.1038/onc.2009.116

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  • DOI: https://doi.org/10.1038/onc.2009.116

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