Classic Signaling Pathway Holds the Key to Prostate Cancer Progression

Levels of phosphorylated/activated AMPK correlate with prostate cancer progression in patients.
Approximately 1 out of every 6 American men will be diagnosed with prostate cancer, and this year alone there are expected to be nearly a quarter of a million new cases diagnosed, making prostate cancer the most common malignancy among men in the United States.  Center for Nuclear Receptors & Cell Signaling (CNRCS) Assistant Professor Daniel Frigo and his research team recently published a study investigating the processes through which androgen receptors affect prostate cancer progression.  The publication, “Androgens Regulate Prostate Cancer Cell Growth via an AMPK-PGC-1α-Mediated Metabolic Switch,” featured online in Oncogene, illuminates a known metabolic pathway as a potential novel therapeutic target.

Although it is well established that the androgen receptor is important for prostate cancer progression, it is unclear what drives this process.  Frigo and his team demonstrated in this study that androgens take control of the AMPK signaling cascade, a master regulator of metabolism, to increase prostate cancer cell growth.

“The androgen signaling cascade is important for understanding early and late-stage prostate cancer progression. We found that when androgens activated this signaling pathway, it hijacked normal conditions, allowing the tumor to use diverse nutrients to the detriment of the patient,” says Frigo. “These results emphasize the potential utility of developing metabolic-targeted therapies directed toward this signaling cascade for the treatment of prostate cancer. We look forward to exploring this and other metabolic pathways further in order to develop the next generation of cancer therapies.”

CNRCS graduate students directly contributed to this study, working alongside postdoctoral fellows and collaborators outside the Center. This research was supported by the National Institutes of Health, Department of Defense, Texas Emerging Technology Fund, and Golfers Against Cancer.

Established in 2009, UH’s Center for Nuclear Receptors and Cell Signaling (CNRCS) is a leading component of the UH Health initiative. Led by Jan-Åke Gustafsson, a National Academy of Sciences member and world-renowned expert in the field of nuclear receptors, CNRCS researchers are involved in many aspects of nuclear receptor research, all focused on understanding the roles of these receptors in health and disease. CNRCS researchers are working toward the goal of finding new treatments for an array of significant diseases including cancer, diabetes, metabolic syndrome and neurological disorders. Working from the center’s world-class labs, the researchers combine interdisciplinary research and dynamic collaboration with the Texas Medical Center and industry partners.