Genomic Deletion of PFKFB3 Decreases In Vivo Tumorigenesis

• Published in: Cancers Vol. 16; no. 13; p. 2330
• Main Authors: Imbert-Fernandez, Yoannis, Chang, Simone M, Lanceta, Lilibeth, Sanders, Nicole M, Chesney, Jason, Clem, Brian F, Telang, Sucheta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-06-2024
• Subjects: 6-Phosphofructo-2-kinase; Animal models; Antibodies; Cancer; Cell division; Clonal deletion; Cloning; Cyclin-dependent kinases; Embryogenesis; Energy metabolism; Enzymes; Fibroblasts; Gene deletion; Genetic crosses; Genomics; Glucose; Glucose metabolism; Glycolysis; Kinases; Metabolism; Phosphorylation; Proenzymes; Proteins; Transformed cells; Transgenic mice; Tumorigenesis; St Louis Missouri; United States > US; lung cancer; Erbb2; Ras; glycolysis; breast cancer; metabolism; phosphofructokinase; glucose metabolism
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16132330

Rapidly proliferative processes in mammalian tissues including tumorigenesis and embryogenesis rely on the glycolytic pathway for energy and biosynthetic precursors. The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) plays an important regulatory role in glycolysis by activating the key rate-limiting glycolytic enzyme, 6-phosphofructo-1-kinase (PFK-1). We have previously determined that decreased PFKFB3 expression reduced glycolysis and growth in transformed cells in vitro and suppressed xenograft growth in vivo. In earlier studies, we created a constitutive knockout mouse to interrogate the function of PFKFB3 in vivo but failed to generate homozygous offspring due to the requirement for PFKFB3 for embryogenesis. We have now developed a novel transgenic mouse model that exhibits inducible homozygous pan-tissue
gene deletion (
). We have induced
genomic deletion in these mice and found that it effectively decreased PFKFB3 expression and activity. To evaluate the functional consequences of
deletion in vivo, we crossed Cre-bearing
mice with oncogene-driven tumor models and found that
deletion markedly decreased their glucose uptake and growth. In summary, our studies reveal a critical regulatory function for PFKFB3 in glycolysis and tumorigenesis in vivo and characterize an effective and powerful model for further investigation of its role in multiple biological processes.