Researchers at the University of Michigan and the University of Foggia in Italy recently revealed that an osteogenic factor called Runx2 is linked to aggressive prostate cancer development. The study is entitled “Role of Runx2 phosphorylation in prostate cancer and association with metastatic disease” and was published in the journal Oncogene.
Prostate cancer is a curable cancer and the second most common cancer in men, with almost one million new cases diagnosed every year worldwide. In the United States, it is estimated that 221,000 new cases will be diagnosed in 2015, resulting in approximately 27,500 deaths. Prostate cancer can range from slow-growing tumors, which are more common, to rapidly progressing aggressive tumors. An early diagnosis of the disease is crucial for improved disease outcomes and survival.
“(In the context of prostate cancer) there’s a big interest in trying to find biomarkers to discriminate between aggressive and nonaggressive disease,” said the study’s senior author Dr. Renny Franceschi in a news release. Biomarkers are indicators of abnormal conditions or functions in the body, including the predisposition to certain diseases.
The transcription factor Runx2 is linked to bone development, where it is activated by a process called phosphorylation (addition of phosphate groups). Curiously, Runx2 has been reported to be abnormally expressed in prostate cancer and to be associated to cancer spread (metastasis). The research team hypothesized that phosphorylation of the Runx2 protein alters its structure and activates certain genes in both bone and prostate cells, yielding different outcomes. Their idea was that while Runx2 and activated genes are required for bone formation, in prostate cancer cells Runx2 activates genes linked to tumor growth and metastasis.
In order to test their hypothesis, researchers inhibited Runx2 phosphorylation in prostate cancer cells and found that cancer growth was reduced. By analyzing Runx2 phosphorylation status in tissue samples from 129 prostate cancer patients, researchers found that normal prostate tissue, benign prostate tissue and inflamed prostate tissue (prostatitis) had little or no Runx2 phosphorylation, while high levels of Runx2 phosphorylation were found to be associated with invasive prostate cancer and lymph node metastases, suggesting that Runx2 phosphorylation is related to prostate cancer induction and progression to more aggressive forms.
The research team concluded that Runx2 phosphorylation is linked to prostate cancer growth and could be used as a potential diagnostic biomarker to assess disease severity and a possible therapeutic target. “If this biomarker [Runx2] does indeed control the growth of prostate cells, it’s a new signal that’s not been seen before and could provide a potential new drug target for prostate cancer,” said Dr. Franceschi. “It could also be a potential biomarker to discriminate between fast and slow growing tumors.”
The team’s next goal is to establish a cause-effect link between Runx2 phosphorylation and prostate cancer.