Two faculty members from the Department of Internal Medicine and a professor of pathology at Yale School of Medicine will conduct research funded by an R01 grant by the National Institutes of Health into whether a liver-derived hormone affects renal cell carcinoma, the most common form of kidney cancer.
The kidney is one of the two organs in the body that can synthesize new glucose through a process known as gluconeogenesis, but the impact of this process in renal cell carcinoma is not known. Their proposal will test whether, and how, a metabolic stress signal, fibroblast growth factor-21 (FGF-21), drives renal cell carcinoma by increasing renal glucose production.
The investigators have shown that FGF-21 promotes kidney glucose production through a liver-central nervous system-kidney axis. “In people with renal cell carcinoma, high serum FGF-21 concentrations are correlated with poorer prognosis, but we don’t know why,” Perry said. “In the R01 proposal, we hypothesize that FGF-21 drives RCC progression by increasing renal glucose production, and that increased glucose fuels tumor progression.”
The study will use genetic and pharmacologic models and tracer analysis – a method that Perry and colleagues previously developed – to document kidney-specific gluconeogenesis rates in mice with kidney cancer, and link alterations in renal glucose production to renal cell carcinoma progression for the first time. A goal of the research is to identify FGF-21 as a potential therapeutic target for kidney cancer.
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