In normal skin cells or HOXA9-reconstituted cSCC cells, HOXA9 interacts with CRIP2 and epigenetically represses HIF-1α expression, which leads to the replacement of HIF-1α by the HOXA9-CRIP2 complex at the promoter regions and inhibits the expression of glycolytic genes, such as HK2, GLUT1, and PDK1. This epigenetic replacement of HIF-1α by HOXA9 is critical for subverting tumor cell metabolism from aerobic glycolysis to OXPHOS and the inhibition of tumor growth. The gene discussed is HK2; the disease is neoplasm.