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March 18, 2013   Columns Articles | Research News | New drug targets found for treatment of prostate cancer

New drug targets found for treatment of prostate cancer

March 18, 2013

Prostate cancer cells need certain enzymes to grow tumors, and an often overlooked enzyme—Pak1—is key for their growth, according to new UGA research.

The study, published in the Journal of Biological Chemistry, was the first to show the importance of Pak1, the p21 activated kinase-1, in prostate cancer and reveal its therapeutic potential for the prevention of prostate tumor growth and spread of cancer cells from the prostate to the bloodstream.

"Many people thought Pak1 was not important for prostate physiology and pathology because its expression in the prostate is very little," said Somanath Shenoy, an assistant professor in the College of Pharmacy, who is the study's lead author. "Our studies identified that Pak1 expression goes up as the prostate cancer progresses and is very high in advanced, or metastatic, prostate cancer."

Using biochemical, molecular biology and pharmacological approaches, Shenoy's research team showed that Pak1 is essential not only for prostate tumor growth but also for cancer cells to break into the bloodstream-by breaking the endothelial-barrier-and further metastasis to distant tissues such as bone.

Highly invasive prostate cancer cells express significantly higher levels of Pak1 protein compared to non-invasive prostate cancer cells, Shenoy said. Prostate tumor tissues and prostate cancer metastasized to the lungs showed higher expression of Pak1 compared to normal tissues. And Pak6 protein expression levels did not change with the invasive/metastatic potential of the cancer cells or tumors. Elevated Pak1 levels in hormone-insensitive prostate cancer cells enhanced their invasive potential.

"Our observations suggest that although some level of functional redundancy exists between Pak1 and Pak6 in prostate cancer cells, targeting Pak1 is a potential option for the management of prostate tumor growth, microinvasion and metastasis," Shenoy said.

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