Could a common natural sweetener be silently fueling the spread of cancer?
HyeYoung Nam, Ph.D., Instructor in the UAB Department of Urology, has been awarded an O’Neal NextGen Faculty Development award from the O'Neal Comprehensive Cancer Center (OCCC) for her study, “Altered fructose metabolism drives renal cancer tumorigenesis by promoting lipolysis.”
The O’Neal NextGen Faculty Development Award supports “early career faculty at the Instructor rank at UAB within the faculty member’s cancer research discipline and facilitates transition into a tenure-track faculty role,” according to the OCCC website.
The department and OCCC will provide $70,000 each to support the development of her independent research.
"Over the past 50 years, the rising consumption of fructose—a sweet sugar found in many fruits and vegetables—has paralleled increasing rates of obesity and certain cancers,” Nam said. “ALDOB, an enzyme crucial for fructose metabolism, is lost in common kidney and other obesity-related cancers, impairing fructose processing. We propose that ALDOB loss enhances fructose-driven tumor progression in renal cancer."
Nam describes her research and how the findings on ALDOB loss and fructose metabolism could reveal new insights into tumor progression in renal cancer.
The role of ALDOB in fructose metabolism
Nam: ALDOB, or fructose-1,6-bisphosphate aldolase, is an enzyme essential for fructose metabolism, particularly in the liver and kidney. It plays a key role in the second step of fructolysis. Previous research shows that ALDOB expression is lost in common kidney and other obesity-related cancers, such as gastric and liver, impairing fructose metabolism. Despite these findings, the impact of ALDOB loss on fructose-driven tumorigenesis remains unexplored. We propose the novel hypothesis that ALDOB loss promotes fructose-mediated tumor progression in renal cancer.
What motivated you to pursue this specific area of research?
Nam: While the NCI has identified 13 malignancies associated with obesity, mechanistic insight into the link between obesity and cancer remains poorly understood. We have recently reported that ALDOB is lost in renal cancer in the Molecular Cancer Research (MCR) paper. Kaplan-Meier analysis indicates that lower ALDOB expression is correlated with worse overall survival in clear cell renal cell carcinoma (ccRCC) patients. However, the molecular mechanism underlying the effect of fructose-mediated tumorigenesis in renal cell carcinoma (RCC) is poorly understood.
We expect the current proposal will elucidate the role of fructose in malignancies in the context of ALDOB loss and determine the biological significance of ALDOB on tumor biology. A better understanding of the molecular mechanism underlying fructose-mediated tumorigenesis in the context of ALDOB loss is important, given the high rates of obesity in the United States and that ALDOB loss is found in multiple obesity-associated cancers.
What are the primary goals and objectives of your study?
Nam: This research will determine whether added fructose promotes renal cancer tumor progression in an animal model. Second, we will investigate the molecular mechanisms that may underlie fructose's influence on tumor progression. Finally, we will study whether suppressing fructose metabolism can suppress tumor progression.
What methodologies or techniques will you be using in your research?
We will assess the effect of fructose on RCC tumorigenesis in patient-derived xenograft (PDX) models. PDX tumors will be established in NSG mice, and then mice will be randomly fed a modified AIN-93G diet, either a fructose-restricted (ND) or high-fructose diet (HFD). Longitudinal tumor volume will be measured weekly.
What are the potential implications of your research findings for the scientific community and public health?
Nam: The proposed studies will provide new insight into the biological basis of fructose-driven tumor progression and identify a novel role for ALDOB in tumor biology through its suppression of tumor phenotypes. Finally, the proposed research will provide a rationale for the further investigation of fructose-mediated tumor progression in renal cancer as a biomarker with clinical applications.