Abstract
Cancer cells perform a metabolic rewiring to sustain an increased growth rate and compensate for the redox stress caused by augmented energy metabolism. The metabolic changes are not the same in all cancers. Some features, however, are considered hallmarks of this disease. As an example, all cancer cells rewire the amino acid metabolism for fulfilling both the energy demand and the changed signaling routes. In these altered conditions, some amino acids are more frequently used than others. In any case, the prerequisite for amino acid utilization is the presence of specific transporters in the cell membrane that can guarantee the absorption and the traffic of amino acids among tissues. Tumor cells preferentially use some of these transporters for satisfying their needs. The evidence for this phenomenon is the over-expression of selected transporters, associated with specific cancer types. The knowledge of the link between the over-expression and the metabolic rewiring is crucial for understanding the molecular mechanism of reprogramming in cancer cells. The continuous growth of information on structure–function relationships and the regulation of transporters will open novel perspectives in the fight against human cancers.
Highlights
It is well established that the metabolism of cancer cells is profoundly altered with respect to their normal counterparts
This is in line with the pleiotropic functions of CD98 ranging from the interaction with other members of the SLC7 family to the activation/regulation of cell pathways which are independent on amino acid transport and metabolism [177]
The roles played by SNAT2 in cancer rewiring may be various: (i) providing cells with proline for epigenetic control; (ii) providing cells with glutamine for energy metabolism; (iii) providing amino acids for signaling purposes merging the function of SLC38A9 in the lysosomal membrane; (iv) accumulating amino acids for protein synthesis and energy metabolism due to the concentrative transport mechanism (Figure 2)
Summary
It is well established that the metabolism of cancer cells is profoundly altered with respect to their normal counterparts. Cells 2020, 9, 2028; doi:10.3390/cells9092028 www.mdpi.com/journal/cells glutamine, glutamate, leucine, aspartate, asparagine, methionine, and serine [1,2,3,12] Tricarboxylic acid cycles invasion and metastasis; in grey, amino acids mainly involved in apoptosis; in green, amino acids reactions are represented by green arrows conducting to the respective intermediate products. The dotted black arrows represent acids is the over-expression of the membrane transporters responsible for their absorption from the non-TCA reactions or pathways, respectively. Amino acids are cyclic pathways are depicted in green or blue, respectively; the urea cycle which is partly represented by the three letter codes and are depicted in blue except for the lysosomal (gray membrane) mitochondrial and partly cytosolic is depicted in the two colors. AA(0,+); isocitrate (ICit); CAT stands for the CAT1,2 and 3 isoforms of transporters
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