The Fer tyrosine kinase acts as a downstream interleukin-6 effector of androgen receptor activation in prostate cancer

Joice Rocha; Fatima Z Zouanat; Amina Zoubeidi; Lucie Hamel; Tarik Benidir; Eleonora Scarlata; Fadi Brimo; Armen Aprikian; Simone Chevalier

doi:10.1016/j.mce.2013.07.017

The Fer tyrosine kinase acts as a downstream interleukin-6 effector of androgen receptor activation in prostate cancer

Mol Cell Endocrinol. 2013 Dec 5;381(1-2):140-9. doi: 10.1016/j.mce.2013.07.017. Epub 2013 Jul 30.

Authors

Joice Rocha¹, Fatima Z Zouanat, Amina Zoubeidi, Lucie Hamel, Tarik Benidir, Eleonora Scarlata, Fadi Brimo, Armen Aprikian, Simone Chevalier

Affiliation

¹ Urologic Oncology Research Group, Departments of Surgery (Urology Division), Medicine, and Oncology, McGill University Health Center (MUHC) Research Institute (RI), Canada.

PMID: 23906537
DOI: 10.1016/j.mce.2013.07.017

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.

Keywords: Androgen independence; Androgen receptor; Castration resistance; Fer tyrosine kinase; IL-6/STAT3; Tyrosine phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Interleukin-6 / metabolism*
Male
Phosphorylation
Prostate-Specific Antigen / metabolism
Prostatic Neoplasms, Castration-Resistant / enzymology*
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational
Protein-Tyrosine Kinases / chemistry
Protein-Tyrosine Kinases / physiology*
Receptors, Androgen / chemistry
Receptors, Androgen / genetics
Receptors, Androgen / metabolism*
STAT3 Transcription Factor / metabolism

Substances

IL6 protein, human
Interleukin-6
Receptors, Androgen
STAT3 Transcription Factor
STAT3 protein, human
proto-oncogene protein c-fes-fps
Protein-Tyrosine Kinases
Prostate-Specific Antigen