Trends in Endocrinology & Metabolism
ReviewA two-front nutritional environment fuels colorectal cancer: perspectives for dietary intervention
Section snippets
The colonic microenvironment
A lifestyle change may prevent 30–50% of cancer deaths, including those from CRC [1]. Diet determines, directly and indirectly, the nutritional environment of colon epithelia and colon cancer cells. Food provides energetic fuel, building blocks, antioxidants, and cofactors, which are absorbed, circulated, stored, and metabolized in different tissues. At the cell level, intertwined metabolic pathways result in energy and building blocks. The balance between and rate of these pathways are
Two-front nutrient supply
The metabolism of colon (cancer) cells is influenced by the available nutrients at either the colonic lumen (apical) or blood and lymph vessels (serosal). This two-front nutrient supply is dictated by food intake, digestion, absorption, storage, metabolism, and release taking place in peripheral organs (Figure 1). At the level of the colon epithelium, these individual-level processes result in an interplay of luminal content, gut microbiota, and serosal nutrients.
On the serosal side,
The unique bioenergetics of the colon cell from cancer initiation to progression
CRC initiates and progresses at the intersection of the two-front nutritional environment. Different cell types are involved, which display differential metabolic routes. Here, we discuss the main metabolic differences between colon (cancer) cell types, which may expose their vulnerabilities. However, investigating colon (cancer) metabolism and the contribution of diet in the two-front nutritional environment with representative models and research methods remains challenging (Box 1).
Impact of dietary factors
The metabolic profile of each colonic cell type creates opportunities to target (colon) cancer bioenergetics by specific dietary interventions (Figure 3). So far, these diets are adapted at the macronutrient level and, consequently, target the demands for glucose, AAs, and FAs for rapid cell proliferation, either directly or indirectly.
Concluding remarks
During CRC initiation and progression, different cell types reside at specific tissue locations, and interact and adapt to the colonic nutritional two-front supply, which alters their bioenergetic status and cancer properties. In this context, nutritional intervention may offer novel therapeutic approaches but is hampered by the functional role of each nutrient of the complex cocktail of structurally different nutrients, which may contribute to CRC prevention or progression by diverse metabolic
Acknowledgments
E.A. is holder of a doctoral (PhD) grant Fundamental Research of Research Foundation-Flanders (FWO Vlaanderen; 1169420N).
Declaration of interests
No interests are declared.
Glossary
- Anoikis
- a type of cell death that is triggered when cells detach from their matrix and neighbor cells.
- Autophagy
- a regulated mechanism that allows the breakdown of dysfunctional cells and recycles cellular nutrients to surrounding cells [44].
- Epithelial–mesenchymal transition (EMT)
- process occurring in later cancer stages by which epithelial cells gain mesenchymal cell characteristics, including reduced cell–cell adhesion and increased invasiveness.
- Glutaminolysis
- metabolic process in which α-KG is
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