Evidence of Glucose and Lipid Metabolism Associated Carcinogenesis in Digestive System: from Molecular Mechanisms to Translational Medicine

In the past decades, the reprogramming of glucose and lipids metabolism has been recognized as the hallmark of malignancies. Tumor cells preferably exhibit dysregulated glycolysis (Warburg effect), gluconeogenesis, and lipid uptake/storage/synthesis, while immune cells (macrophages and T cells) in the tumor microenvironment (TME) manifest distinct glucose metabolic patterns. The metabolic involvement is also represented as the aberrant activation of various enzymes or transporters linking to glucose and lipids in various cancers. Such alterations are especially evident in gastrointestinal cancers like hepatocellular carcinoma, gastric and colon cancer, partially owing to the principal competence of gastrointestinal organs for food digestion, absorption and conversion. As the major nutrient sources, glucose and lipids not only maintain tumor survival via energy supply, but also function as signaling molecules to drive oncogenic events. In another aspect, heterogeneous alterations of oncometabolite pathways like PI3K-AKT, mTORC, and Ras reversely facilitate abnormal glucose uptake, glycolysis, and de novo lipogenesis, thus promoting tumor progression. Basically, glucose and lipid metabolism are - correlated rather than separated processes, for glucose generates and conveys citrate for the synthesis of fatty acids and cholesterol, and mediates lipids glycosylation through hexosamine pathways. However, the specific regulatory mechanisms of metabolic crosstalk and their contribution for malignancy deterioration remain poorly understood at the current stage. Better description of such mechanisms will probably provide potential targets and rationale basis for novel therapeutic strategies.

This Research Topic is aiming at presenting the recent advances of glucose/lipids associated carcinogenesis in digestive system through basic research, and potential therapeutic applications through translational medicine.

We welcome contributions including Original Research, Review, Mini-review, Clinical Trial, and Perspective Articles covering, but not limited to the following subjects:

• Innovative perspectives of glucose or lipid metabolism associated oncology in digestive system.
• The metabolic influence of glucose or lipids on tumor microenvironment (from parenchymal cells to stromal cells) in gastrointestinal cancers.
• Genetic/transcriptional/post-transcriptional alterations and specific regulatory mechanisms leading to glucose or lipid metabolism dysfunction and the concomitant carcinogenesis in digestive system.
• Integrated elucidation of the peculiarity, relevance and crosstalk between glucose and lipid metabolism, which synergistically contributes to tumorigenesis in digestive system.
• Potential diagnostic and therapeutic targets or methodologies rooted in glucose and lipid metabolism for gastrointestinal cancer management.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.