Journal article
Functional screen identifies kinases driving prostate cancer visceral and bone metastasis
Proceedings of the National Academy of Sciences - PNAS, v 113(2), pp E172-E181
12 Jan 2016
PMID: 26621741
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mutationally activated kinases play an important role in the progression and metastasis of many cancers. Despite numerous oncogenic alterations implicated in metastatic prostate cancer, mutations of kinases are rare. Several lines of evidence suggest that nonmutated kinases and their pathways are involved in prostate cancer progression, but few kinases have been mechanistically linked to metastasis. Using a mass spectrometry-based phosphoproteomics dataset in concert with gene expression analysis, we selected over 100 kinases potentially implicated in human metastatic prostate cancer for functional evaluation. A primary in vivo screen based on overexpression of candidate kinases in murine prostate cells identified 20 wild-type kinases that promote metastasis. We queried these 20 kinases in a secondary in vivo screen using human prostate cells. Strikingly, all three RAF family members, MERTK, and NTRK2 drove the formation of bone and visceral metastasis confirmed by positron-emission tomography combined with computed tomography imaging and histology. Immunohistochemistry of tissue microarrays indicated that these kinases are highly expressed in human metastatic castration-resistant prostate cancer tissues. Our functional studies reveal the strong capability of select wild-type protein kinases to drive critical steps of the metastatic cascade, and implicate these kinases in possible therapeutic intervention.
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Details
- Title
- Functional screen identifies kinases driving prostate cancer visceral and bone metastasis
- Creators
- Claire M Faltermeier - University of California, Los AngelesJustin M Drake - University of California, Los AngelesPeter M Clark - University of California, Los AngelesBryan A Smith - University of California, Los AngelesYang Zong - Howard Hughes Medical InstituteCarmen Volpe - University of California, Los AngelesColleen Mathis - University of California, Los AngelesColm Morrissey - University of WashingtonBrandon Castor - University of California, Los AngelesJiaoti Huang - University of California, Los AngelesOwen N Witte - aMolecular Biology Institute, University of California, Los Angeles, CA 90095;
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 113(2), pp E172-E181
- Publisher
- PNAS
- Grant note
- 2P30CA016042-39 / NCI NIH HHS R01 CA181242 / NCI NIH HHS Howard Hughes Medical Institute T32 CA009056 / NCI NIH HHS T32 CA00912 / NCI NIH HHS P50 CA097186 / NCI NIH HHS R01 CA195505 / NCI NIH HHS R25 CA098010 / NCI NIH HHS 5R01CA172603-02 / NCI NIH HHS 1R01CA195505 / NCI NIH HHS P50CA97186 / NCI NIH HHS P01CA085859 / NCI NIH HHS R01 CA172603 / NCI NIH HHS P50 CA092131 / NCI NIH HHS P01 CA085859 / NCI NIH HHS R25T CA098010 / NCI NIH HHS T32 CA009120 / NCI NIH HHS P30 CA016042 / NCI NIH HHS 1R01CA181242-01A1 / NCI NIH HHS P50 CA086306 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000367881500012
- Scopus ID
- 2-s2.0-84954530972
- Other Identifier
- 991019356342504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology