Functional screen identifies kinases driving prostate cancer visceral and bone metastasis
Abstract
Therapies are urgently needed to treat metastatic prostate cancer. Mutationally activated and wild-type kinases such as BCR-ABL and BTK are effective therapeutic targets in multiple cancers. Genetically altered kinases are rare in prostate cancer. Wild-type kinases may be implicated in prostate cancer progression, but their therapeutic potential in metastatic prostate cancer remains unknown. Using phosphoproteomics and gene expression datasets, we selected 125 wild-type kinases implicated in human prostate cancer metastasis to screen for metastatic ability in vivo. The RAF family, MERTK, and NTRK2 drove prostate cancer bone and visceral metastasis and were highly expressed in human metastatic prostate cancer tissues. These studies reveal that wild-type kinases can drive metastasis and that the RAF family, MERTK, and NTRK2 may represent important therapeutic targets.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 30, 2015
- Source ID
- 10.1073/pnas.1521674112
Entities
People
- Brandon Castor
- Bryan A. Smith
- Carmen Volpe
- Claire M. Faltermeier
- Colleen Mathis
- Colm Morrissey
- Jiaoti Huang
- Justin M Drake
- Owen N Witte
- Peter M. Clark
- Yang Zong
Organizations
- American Association for Cancer Research
- Howard Hughes Medical Institute
- National Cancer Institute
- United States Department of Defense
- University of California
- University of California, Los Angeles
- University of Washington