1. The Fer tyrosine kinase acts as a downstream interleukin-6 effector of androgen receptor activation in prostate cancer
- Author
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Simone Chevalier, Fadi Brimo, Lucie Hamel, Amina Zoubeidi, Fatima Z. Zouanat, Armen Aprikian, Eleonora Scarlata, Tarik Benidir, and Joice Rocha
- Subjects
Male ,STAT3 Transcription Factor ,urologic and male genital diseases ,SH2 domain ,Biochemistry ,Prostate cancer ,chemistry.chemical_compound ,Endocrinology ,Cell Line, Tumor ,medicine ,Humans ,Protein Interaction Domains and Motifs ,Tyrosine ,Phosphorylation ,STAT3 ,Interleukin 6 ,Molecular Biology ,biology ,Interleukin-6 ,Tyrosine phosphorylation ,Prostate-Specific Antigen ,Protein-Tyrosine Kinases ,medicine.disease ,Androgen receptor ,Gene Expression Regulation, Neoplastic ,Prostatic Neoplasms, Castration-Resistant ,chemistry ,Receptors, Androgen ,biology.protein ,Cancer research ,Protein Processing, Post-Translational - Abstract
Castrate-resistant prostate cancer (CRPC) is invariably lethal and still poorly understood. IL-6/pSTAT3 appears critical as elevated IL-6 and pSTAT3 correlate with CRPC and poor prognosis. We previously reported on the Fer tyrosine kinase being an integral component of the IL-6 pathway in PC by controlling STAT3. Since IL-6 also controls androgen receptor (AR) signaling via pSTAT3, we tested if Fer participates in this cross-talk. We report for the first time that in addition to STAT3, Fer is required for IL-6 mediated AR activation by phosphorylating AR tyrosine 223 and binding via its SH2 domain. Fer controls IL-6 induced growth response and PSA expression, while modestly contributing to EGF and IGF-1 effects. Finally, Fer, AR and pSTAT3 co-localize in the PC cell nucleus, including in prostate tissues from CRPC patients. Altogether these findings support a Fer contribution to aberrant AR signaling via pSTAT3 cross-talks during CRPC progression.
- Published
- 2013