title: IL-6/STAT3/ARF: the guardians of senescence, cancer progression and metastasis in prostate cancer.
abstract: Prostate cancer is one of the most prevalent forms of cancer in men worldwide. It remains a clinical challenge to identify lethal metastatic prostate cancers, which escape standard therapeutic intervention. Aberrant interleukin-6 (IL-6) / signal transducer and activator of transcription-3 (STAT3) signalling and loss of p53 occur during prostate cancer progression to metastatic disease. The abnormality of the IL-6/STAT3/p53 axis is frequently accompanied by other genetic alterations; however, its potential role as an important mediator of oncogenic reprogramming, invasion and metastatic transformation remains unknown. The failure of anti-IL-6 treatments is still unexplained and may be due to an incomplete understanding of the mechanism of the in vivo role of IL-6/STAT3 in prostate cancer. The identification of the alternative reading frame protein (ARF) / murine double minute protein (MDM2) / p53 tumour suppressor pathway potentially involving the IL-6/STAT3 axis as a restricting factor in prostate cancer deficient in the tumour suppressor phosphatase and tensin homologue (PTEN) opened new avenues to currently available therapies. This review summarises the current knowledge on the role of crucial pathways driving prostate cancer progression as well as metastatic disease and discusses the potential use of novel specific target molecules and how it can be exploited to avoid overtreatment and increase quality of life.
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Medical University of Vienna, Austria; Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Pencik
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Wiebringhaus
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.affiliation: Department of Urology, Medical University of Innsbruck, Vienna, Austria.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Medical University of Vienna, Austria; Clinical Institute of Pathology, Medical University of Vienna, Austria; Depatment of Pathology of Laboratory Animals (UPLA), University of Veterinary Medicine Vienna, A.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy; D011788:Quality of Life; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human