Insights into the Role of Metabolic Reprogramming in Cancer Metastasis

Metabolic reprogramming is an emerging hallmark of cancer cells. In 1920s, Otto Warburg first discovered that cancer cells maintain high levels of glycolysis for ATP production, regardless of oxygen availability. From then on, studies began to focus on cancer-associated metabolic reprogramming within crucial metabolic pathways including altered metabolism of glucose, lipids, and amino acids to explore potential metabolic vulnerabilities during cancer progression. A general characteristic of cancer cells is their capability to obtain nutrients from a nutrient-deprived environment to sustain their transformed state, build biomass, and increase invasive potential. In the tumor microenvironment, cancer cells have a complex interplay with tumor-associated stromal cells, such as immune cells, fibroblasts and endothelial cell. For example, growing evidences have shown that metabolic alteration occurring in cancer cells can also impact on immune cell functionality and contribute to tumor immune evasion. Besides, metabolic reprogramming is not restricted to tumor cells. Under hypoxic and nutrient-deprived environment, these tumor-associated stromal cells also undergo complex metabolic reprogramming, which may alter their function and subsequently influence cancer development. Specifically, the altered metabolic phenotype of immune cells including macrophages, Treg, dendritic cells, and T lymphocytes may further shape the immune response, which may provide new insights to target metabolism for immunotherapy.

Metastasis is regarded as a complex multistep process that tumor cells leave the primary site and form a distant lesion in the secondary site. Although advanced diagnostic and treating approaches have been developed, metastasis is still the leading cause of death for majority of cancers. Metabolic reprogramming is required for the enhanced invasive and metastatic potential of cancer cells. Thus, exploring potential metabolic vulnerabilities may provide fundamental knowledge for blocking tumor metastasis, which may be valuable for the diagnosis and management of malignant tumors.

This Research Topic aims to provide our current understanding of the role of metabolic reprogramming in the context of metastasis. We welcome Original Research articles and Reviews on the subtopics below:

• Crucial metabolic pathways including altered metabolism of glucose, lipids, and amino acids;
• Mitochondrial energy metabolism and metastasis;
• The metabolic features and altered function of cancer-associated stromal cells;
• The association between metabolic reprogramming and cancer stem cells (CSCs);
• Cancer metabolism and immune evasion;
• Metabolic features of different metastatic steps (e.g. Epithelial-mesenchymal transition or colonization);
• Drugs that targets cancer metabolism and metastasis.