Several studies in recent years have unveiled the crucial role of metabolic reprogramming in tumorigenesis and tumour progression, yielding a series of new therapeutic targets and strategies.34–37 Our previous metabolomics study of clinical CRC tissue samples revealed glucose scarcity in the TME.27 In the current study, we demonstrated that low-glucose conditions serve as an upstream signal to stimulate the AMPK/CREB1 signalling pathway in CRC cells, subsequently upregulating GLUT3, a transmembrane transporter with a high affinity for glucose. Here, CREB1 is linked to neoplasm.