The Fer tyrosine kinase acts as a downstream interleukin-6 effector of androgen receptor activation in prostate cancer
| Autor: | Simone Chevalier, Fadi Brimo, Lucie Hamel, Amina Zoubeidi, Fatima Z. Zouanat, Armen Aprikian, Eleonora Scarlata, Tarik Benidir, Joice Rocha |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
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 |
| Zdroj: | Molecular and cellular endocrinology. 381(1-2) |
| ISSN: | 1872-8057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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