A team of researchers from Wayne State University was 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., professor of molecular medicine and genetics, and biochemistry, microbiology and immunology at Wayne State University’s School of Medicine, goals to determine 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 often known as the Warburg effect – and evasion of apoptosis.
In keeping with the National Cancer Institute of the National Institutes of Health, in 2023 it was estimated that greater than 288,000 men could be diagnosed with prostate cancer and 34,700 would die in the US, making it the second commonest cancer in men. Previously decade, diagnoses of prostate cancer increased from 3.9% to eight.2%, with African American men having the best incidence and mortality rates of the disease in comparison with 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 this hypothesis.
The research team proposes that cytochrome c transitions from a non-acetylated form in a traditional prostate to a K53-acetylated cytochrome c in cancer.
What we’re proposing is that this transition causes switching from aerobic metabolism to Warburg metabolism since the modification renders cytochrome c less effective in transferring electrons within the electron transport chain, and at the identical time making it incapable of triggering apoptosis. 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 resulting in acetylation of cytochrome c, with the last word goal of identifying novel therapeutic targets that might lead to developing a drug to beat treatment resistance as a stand-alone or combination therapy.”
Maik Hüttemann, Ph.D., professor of molecular medicine and genetics, and biochemistry, microbiology and immunology, Wayne State University’s School of Medicine
“This necessary funding from the U.S. Department of Defense supports high-impact research needed to advance our understanding of detect and treat prostate cancer,” said Ezemenari M. Obasi, Ph.D., vice chairman for research at Wayne State University. “The work that Dr. Hüttemann and his collaborators are doing will improve health equity and reduce disparities in prostate cancer and should ultimately enhance the standard and length of life for those impacted by prostate cancer.”
Collaborators on this project include Izabela Podgorski, Ph.D., professor of pharmacology, Wayne State University School of Medicine; Elisabeth Heath, M.D., associate director, Department of Oncology, Wayne State University School of Medicine; Seongho Kim, Ph.D., professor of oncology, Wayne State University School of Medicine; and Dongping Shi, M.D., chief and medical director, Detroit Medical Center Sinai-Grace Hospital.
The grant number for this U.S. Department of Defense grant is HT94252410073.