$1.4 Million Awarded to Karmanos, WSU Researcher to Expand Findings Surrounding Prostate Cancer

A team of researchers at the Barbara Ann Karmanos Cancer Institute and Wayne State University (WSU) were awarded a $1.4 million, three-year grant from the U.S. Department of Defense for the study, “Cytochrome c acetylation drives prostate cancer aggressiveness and Warburg effect.”

The study, led by Maik Hüttemann, Ph.D., Tumor Biology and Microenvironment (TBM) Research Program member at Karmanos, professor of Molecular Medicine and Genetics, and Biochemistry, Microbiology and Immunology at WSU’s School of Medicine, aims to establish the role of the protein cytochrome c, which the team proposes is central in two hallmarks of cancer: switching from aerobic to glycolytic metabolism – also known as the Warburg effect – and evasion of apoptosis.

The National Cancer Institute of the National Institutes of Health estimated that more than 288,000 men would be diagnosed with prostate cancer, and 34,700 would die in the United States in 2023, making it the second most common cancer in men. In the past decade, diagnoses of prostate cancer increased from 3.9% to 8.2%, with African American men having the highest incidence and mortality rates of the disease compared to white, Hispanic and Asian men. Cytochrome c was previously suggested to be a molecular determinant of prostate cancer health disparities, and this study will further explore that hypothesis.

The research team proposes that cytochrome c transitions from a non-acetylated form in a normal prostate to a K53-acetylated cytochrome c in cancer.

“What we are proposing is that this transition causes switching from aerobic metabolism to Warburg metabolism because the modification renders cytochrome c less effective in transferring electrons in the electron transport chain, and at the same time making it incapable of triggering apoptosis,” Dr. Hüttemann said. “Warburg and evasion of apoptosis are two key features of cancer cells. This funding from the Department of Defense will allow us to develop an antibody as a prognostic and diagnostic tool and to mechanistically study the pathways leading to the acetylation of cytochrome c, with the ultimate goal of identifying novel therapeutic targets that could result in developing a drug to overcome treatment resistance as a stand-alone or combination therapy.”

Additional Karmanos research members collaborating on this project include Izabela Podgorski, Ph.D., TBM Research Program member, professor of Pharmacology; Elisabeth Heath, M.D., FACP, medical oncologist, Genitourinary Oncology Multidisciplinary Team leader, associate center director of Translational Science, TBM Research Proram member at Karmanos and professor of Oncology; and Seongho Kim, Ph.D., Molecular Therapeutics Research Program member at Karmanos and professor of Oncology.

The grant number for this U.S. Department of Defense grant is HT94252410073.

Originally published at Today@Wayne.