Table 1.
Main glutamine metabolic pathways activated in CSC, their effects on cancer stemness, stemness markers.
| Cell Type | Gln-Dependent Metabolic Pathway | Impact on Stemness | Stemness Markers |
References |
|---|---|---|---|---|
| Embryonal carcinoma (EC) | GSH biosynthesis | + | Oct4, Nanog, Sox2 Sphere formation |
[35] |
| Triple-negative breast cancer (TNBC) | GSH biosynthesis | + | GD2 Sphere formation |
[36] |
| Prostate cancer | GSH biosynthesis | + | ALDH activity Sphere formation Tumor initiation |
[37] |
| Head and neck squamous cell carcinoma (HNSCC) | GSH biosynthesis | + | CD44v Sphere formation Tumor initiation |
[38] |
| Pancreatic ductal adenocarcinoma (PDAC) | GOT1-dependent NADPH biosynthesis | + | CD44, CD133, ESA, ALDH1 Sphere formation Tumor initiation |
[39] |
| Head and neck squamous cell carcinoma (HNSCC) | glutaminolysis and TCA cycle | + | CD44v | [42] |
| Non-small-cell lung cancer (NSCLC) | IDH2-dependent NADPH biosynthesis | + | Sphere formation | [44] |
| Glioblastoma (GBM) | IDH1-dependent NADPH biosynthesis | + | Sphere formation Tumor initiation |
[48] |
| NSCLC, GBM | GSH-mediated β-catenin stability | + | Side population Sox2, ABCG2 Tumor initiation |
[50] |
| Hepatocellular carcinoma (HCC) | GSH-mediated β-catenin nuclear translocation | + | Oct4, Nanog, Sox2, CD44, CD133, KLF4 Sphere formation |
[51] |
| Epithelial ovarian cancer colorectal cancer (CRC) |
ROS-mediated ERK1/2-dependent DRP1 activation | − | Oct4, Sox2, Nanog, ABCG2, CD44 ALDH activity Sphere formation |
[52] |
| HCC | mitochondrial ATP production | + | P-glycoprotein CD49, CD99, CD34 |
[53] |
| Ovarian clear cell adenocarcinoma (OCCA) Cervical squamous cell carcinoma (CSCC) |
Amino acids biosynthesis | + | Sphere formation | [55] |
| GBM | TCA cycle and amino acids biosynthesis | + | Sphere formation | [56] |
| GBM | Amino acids biosynthesis | + | Sphere formation | [57] |
| GBM | Glutamate biosynthesis | + | Sphere formation | [61] |
| GBM | Nucleotides biosynthesis | + | CD133, Sox2, Olig2 | [63] |
| GBM | Nucleotides biosynthesis | + | Sox2, NES, Olig2 Sphere formation Tumor initiation |
[65] |
| HCC | Nucleotides biosynthesis | − | Oct4, Sox2, KLF4, CD133 Sphere formation |
[66] |
| PDAC | Nucleotides biosynthesis | − | Sphere formation Tumor initiation |
[67] |
| Breast carcinoma NSCLC |
Nucleotides biosynthesis | + | CD44, CD24 Clonogenicity assay |
[68] |
| PDAC | NH4+ production | + | Sphere formation | [75] |
| GBM | IDH1-dependent αKG biosynthesis | + | Sphere formation Tumor initiation |
[48] |
| GBM | αKG-dependent histone demethylation | + | Sphere formation Tumor initiation |
[48] |
| Prostate cancer | αKG-dependent histone demethylation | + | ALDH activity Sphere formation Tumor initiation |
[37] |
| CRC | αKG biosynthesis | − | Lgr5 Organoid formation Tumor initiation |
[81] |
| Melanoma TNBC |
αKG biosynthesis | − | CD271, ABCB5, CD133, Nanog, Sox2, NES, KLF4 | [1] |
| PDAC | TCA cycle | + | CD44 Organoid formation Tumor initiation |
[84] |
| HNSCC | Glutamate biosynthesis and | + | CD44, ALDH | [88] |
+ indicates induction of stemness, – indicates dedifferentiation or loss of stem cells.