Researchers have discovered an unexpected role for the gene STAT3 in prostate cancer progression. While STAT3, controlled by interleukin 6 (IL-6), has an oncogenic role in most cancers, it in fact suppresses tumor growth in prostate cancer. The work was published recently in the journal Nature Communications.
Hyperactive IL-6 cytokine is thought to support tumor growth through its control of STAT3, shown to promote cancer progression in most tumors. Many cancer therapies therefore aim to suppress STAT3 or IL-6. The current study revealed that, within prostate tumors, STAT3 activates the gene p14ARF, which subsequently blocks cell division.
Jan Pencik (Ludwig Boltzmann Institute for Cancer Research, Austria) explained: “Using knockout mice, which are preclinical model organisms, we can link IL-6/Stat3 signaling to ARF, an important gene for cell cycle control and decisions to grow or to arrest. These findings have consequences for prostate cancer metastasis.”
Therefore, p14ARF and STAT3 may be ideal candidates for biomarkers of prostate cancer prognosis, with their presence translating to a much lower risk of tumor metastasis. According to Lukas Kenner (Ludwig Boltzmann Institute for Cancer Research, Austria), these proteins may be twice as accurate (in terms of predictive power) than the previous gold standard.
Particularly given the low mortality rate associated with prostate cancer, these biomarkers could prevent unnecessary interventions with severe adverse events. The findings could also lead to a noninvasive test to replace painful tissue biopsies.
A further implication is that therapies that block IL-6 in other diseases, for example rheumatoid arthritis, could enhance malignancies. Helmut Dolznig (Medical University of Vienna, Austria) concluded: “Applying IL-6/Stat3 blockers to clinical practice might be dangerous for patients with cancerous lesions, further studies are mandatory to assess the possibility of increased cancer risk right now.”