CDT1 and E2F1 synergistically promote the glycolysis and progression of non-small cell lung cancer through the TPX2/AKT pathway.

Emerging data indicate that chromatin licencing and DNA replication factor 1 (CDT1) plays an important role in several cancers. However, it remains unclear whether CDT1 is functionally indispensable in lung cancer. Here, constructing tissue microarrays and performing in vitro and vivo experiments, we showed that CDT1 was significantly overexpressed in lung adenocarcinoma tissues, and its expression level significantly correlated with pathological stage, tumour invasiveness, and overall patient survival. Mechanistic investigations revealed that CDT1 possibly interacted with the transcription factor adenovirus early region 2 binding factor 1 (E2F1), thereby cooperatively enhancing the transcriptional activity of the targeting protein for Xenopus kinesin-like protein 2 (TPX2) gene. This phenomenon subsequently increased the expression of glycolysis-related molecules aldolase C and pyruvate kinase M2 via the PI3K/AKT signalling pathway, which promoted the proliferation and migration of non-small cell lung cancer (NSCLC) cells. Critically, knockdown of TPX2 or treatment with either the AKT pathway inhibitor MK-2206 2HCl or the glycolysis inhibitor AZ33 effectively reversed the promoting effects of CDT1 on AKT pathway activity, glycolytic metabolism, and tumour progression in CDT1-overexpressing NSCLC cells. Collectively, this study elucidates that CDT1 and E2F1 mutually promote the glycolysis and progression of NSCLC cells by activating the TPX2/AKT pathway. These findings provide novel therapeutic targets for refractory NSCLC treatment.