Oncotarget

Research Papers:

Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells

Tanushree Chatterji, Andreas S. Varkaris, Nila U. Parikh, Jian H. Song, Chien-Jui Cheng, Rebecca E. Schweppe, Stephanie Alexander, John W. Davis, Patricia Troncoso, Peter Friedl, Jian Kuang, Sue-Hwa Lin and Gary E. Gallick _

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Oncotarget. 2015; 6:10175-10194. https://doi.org/10.18632/oncotarget.3391

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Abstract

Tanushree Chatterji1,2, Andreas S. Varkaris1, Nila U. Parikh1, Jian H. Song1, Chien-Jui Cheng3,4, Rebecca E. Schweppe5, Stephanie Alexander1,6, John W. Davis7, Patricia Troncoso8, Peter Friedl1,5, Jian Kuang9, Sue-Hwa Lin1,2,10, Gary E. Gallick1,2

1Department 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

2Programs in Cancer Biology and Cancer Metastasis, The University of Texas Graduate School of Biomedical Sciences at Houston, TX, USA

3Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan

4Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

5Division of Endocrinology, Metabolism, and Diabetes, and Department of Pathology, University of Colorado Anschutz Medical Campus, University of Colorado Cancer Center, Aurora, CO, USA

6Department of Cell Biology, Radboud University Medical Center, Nijmegen, the Netherlands

7Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

8Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

9Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

10Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Gary E. Gallick, e-mail: [email protected]

Keywords: FAK, Yes, migration, metastasis, prostate cancer

Received: November 12, 2014     Accepted: February 16, 2015     Published: March 18, 2015

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.


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