Remarkably, even HIF1A knockout cells preserved glycolysis, whereas glycolytic genes were significantly downregulated, indicating HIF-1-independent metabolic compensation.<h4>Conclusion</h4>Our findings position p53 as a temporal gatekeeper and key regulator of hypoxic adaptation in CRC cells, coordinating early gene induction and metabolic responses. The gene discussed is TP53; the disease is colorectal carcinoma.