Cancer cells utilise more nutrients than non-cancerous cells to promote the malignant phenotype. In this study we investigated the metabolic requirements of endometrial cancer; the most common gynaecological malignancy in Australia. Using genetic, metabolic, and biochemical approaches, we revealed that alterations in genes that regulate nutrient uptake and metabolism play a central role in endometrial cancer cell biology. Specifically, glucose transporter 6 (GLUT6) is upregulated in malignant cells of the endometrium and human endometrial cancer cell lines. Functional studies revealed that this glucose transporter supports the glycolytic phenotype and is required for endometrial cancer cell survival. Notably, GLUT6 is not widely expressed in the human body which makes GLUT6 an attractive therapeutic target for this cancer and others in which GLUT6 is upregulated. To further investigate the potential of GLUT6 as an anti-cancer target we created a GLUT6 knockout mouse and are developing small molecule inhibitors of GLUT6.