Chemerin Overexpression in Clear Cell Kidney Cancer: Lipid Metabolism and Tumorigenesis
Posted: Tuesday, May 4, 2021
A recent article published in Cancer Discovery highlighted a mechanistic link between obesity and fat metabolism in patients with clear cell renal cell carcinoma. Scott Welford, PhD, of the University of Miami Miller School of Medicine, Miami, and colleagues examined the role of signaling proteins in modulating communication between tumor cells and adipose tissue and whether this communication drives tumorigenesis. Their findings revealed that overexpression of the adipokine protein chemerin was found in tumor tissues and patient plasma. Consequently, attenuation of chemerin may lead to a significant reduction in lipid deposition and potential tumor cell growth.
“This research provides a biological link between obesity and kidney cancer, suggesting a molecular marker and therapeutic target that can be used to improve the way we currently treat this disease. Targeting this pathway represents an exciting area for future pharmacologic research and development of clinical trials to provide patients with additional treatment options,” said coauthor Mark L. Gonzalgo, MD, PhD, also of the University of Miami.
A multidisciplinary approach was used to investigate the adipose mechanisms involved in tumor activity. The researchers combined single-cell resolution transcriptomic data, metabolomic
analyses, and multiple clear cell renal cell carcinoma model systems. Findings revealed that chemerin is overexpressed in clear cell renal cell carcinoma, likely due to an autocrine-dependent and an obesity-dependent mechanism. They also found that depleting chemerin resulted in “metabolic rewiring,” mitochondrial dysfunction, and ferroptosis. As the secretory nature of chemerin makes it detectable in plasma, monoclonal antibodies may prove to disrupt it, thereby making chemerin a potential diagnostic marker and therapeutic target.
Disclosure: The study authors reported no conflicts of interest.