title: Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells.
abstract: To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration and invasion in vitro, but were also more metastatic to lymph nodes following intraprostatic injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically increased in phosphorylation of FAK Y861. We therefore examined potential alterations in Src family kinases responsible for FAK phosphorylation and determined only Yes expression was increased. Overexpression of Yes in PC3 parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861 phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells decreased migration and decreased lymph node metastasis following orthotopic implantation of into nude mice. In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis. These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Programs in Cancer Biology and Cancer Metastasis, The University of Texas Graduate School of Biomedical Sciences at Houston, TX, USA.
authors: Tanushree
authors: T
authors: Chatterji
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Andreas S
authors: AS
authors: Varkaris
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Nila U
authors: NU
authors: Parikh
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Jian H
authors: JH
authors: Song
authors: Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Chien-Jui
authors: CJ
authors: Cheng
authors: Division of Endocrinology, Metabolism, and Diabetes, and Department of Pathology, University of Colorado Anschutz Medical Campus, University of Colorado Cancer Center, Aurora, CO, USA.
authors: Rebecca E
authors: RE
authors: Schweppe
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Cell Biology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: Stephanie
authors: S
authors: Alexander
authors: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: John W
authors: JW
authors: Davis
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Patricia
authors: P
authors: Troncoso
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Division of Endocrinology, Metabolism, and Diabetes, and Department of Pathology, University of Colorado Anschutz Medical Campus, University of Colorado Cancer Center, Aurora, CO, USA.
authors: Peter
authors: P
authors: Friedl
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Jian
authors: J
authors: Kuang
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Programs in Cancer Biology and Cancer Metastasis, The University of Texas Graduate School of Biomedical Sciences at Houston, TX, USA.|Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Sue-Hwa
authors: SH
authors: Lin
authors: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Programs in Cancer Biology and Cancer Metastasis, The University of Texas Graduate School of Biomedical Sciences at Houston, TX, USA.
authors: Gary E
authors: GE
authors: Gallick
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human
keywords: FAK; Yes; metastasis; migration; prostate cancer