Metabolic reprogramming is an important feature of tumors, and reprogramming of glucose metabolism was the earliest identified marker of metabolic alterations in tumors. The Warburg effect describes the propensity of tumor cells to preferentially metabolize glucose through glycolysis, even in the presence of oxygen, rather than relying on oxidative phosphorylation. This unique metabolic phenotype empowers cancer cells to proliferate and invade indefinitely, inducing metabolic adaptations that provide cancer cells with a survival advantage in hypoxic and nutrient-poor environments. Various mechanisms are able to promote the Warburg effect, and the adverse effects are complex and diverse. This review primarily examines the Warburg effect in tumor cells, and systematically investigates the influence of factors such as glycolytic enzymes, mitochondrial function, tumor microenvironment, and oncogenes on the Warburg effect. It comprehensively summarizes the underlying mechanisms of reactions and corresponding targeted drugs while discussing their potential applications in anticancer therapy. Elevated aerobic glycolysis activity represents a key characteristic of tumor cells, which can offer new insights for early diagnosis and treatment of cancer. Furthermore, in the context of recent research advancements, this review discusses how these insights may contribute to the development of novel therapeutic strategies. which is a difficult and meaningful challenge.

Hepatocellular carcinoma (HCC) is characterized by frequent intrahepatic and distant metastases, resulting in a poor prognosis for patients. Epithelial–mesenchymal transition (EMT) plays a pivotal role in this process. However, the expression of NOP2/Sun RNA methyltransferase 5 (NSUN5) in HCC and its role in mediating EMT remain poorly understood. In this study, clinicopathological analyses are conducted across multiple independent HCC cohorts and induced tumor formation in Nsun5‐knockout mice. The findings reveal an upregulation of NSUN5 expression in tumor tissues; conversely, the absence of Nsun5 hinders the malignant progression of HCC, indicating that NSUN5 may serve as a significant oncogene in HCC. Furthermore, elevated levels of NSUN5 enhance EMT processes within HCC cells. NSUN5‐knockout cells exhibit reduced invasion and migration capabilities under both in vivo and in vitro conditions, while overexpression of NSUN5 yields opposing effects. Mechanistically, high levels of NSUN5 promote the enrichment of trimethylated histone H3 at lysine 4 (H3K4me3) at the promoter region of SMAD3 through recruitment of the WDR5, thereby facilitating HCC metastasis via SMAD3‐mediated EMT pathways. Collectively, this study identifies NSUN5 as a novel driver of metastasis in HCC and provides a theoretical foundation for potential therapeutic strategies against this malignancy.

Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. Ferritinophagy, an autophagy‐dependent process regulating iron metabolism, has emerged as a key contributor to ferroptosis and tumour progression. This study hypothesised that the ferritinophagy‐related gene FTH1 drives HCC pathogenesis by modulating tryptophan metabolism and reactive oxygen species (ROS)‐dependent ferroptosis. To test this, we first analysed TCGA data to identify prognostic ferritinophagy genes, revealing FTH1 as a critical risk factor. Functional experiments using FTH1 ‐knockdown/−overexpressing HCC cell lines and xenograft models demonstrated that FTH1 enhances proliferation, migration, and tumour growth by upregulating CYP1A1/CYP1A2 in the tryptophan pathway, thereby increasing the synthesis of 6‐hydroxymelatonin (6‐HMT). Mechanistically, 6‐HMT suppressed ROS and ferroptosis by inhibiting cytochrome P450 oxidoreductase (POR). Concurrently, intracellular tryptophan levels were found to inhibit NCOA4‐mediated selective autophagy of FTH1, stabilising FTH1 levels and promoting tumour survival. Collectively, our findings establish FTH1 as a central regulator of ferritinophagy in HCC and reveal its dual role in linking tryptophan metabolism to redox homeostasis. This result provides a hint of how FTH1 influences HCC pathogenesis and positions the tryptophan metabolism pathway as a promising therapeutic target.