Table I.
Differences and similarities among bulk cancer cells, CSCs and normal stem cells.
| Pathway | Key molecules | Function | Bulk cancer cells | CSCs | Normal stem cells |
|---|---|---|---|---|---|
| FA synthesis | ACLY | Catalyze citrate converting into acetyl CoA in the cytoplasm | Elevated in gastric adenocarcinoma | Elevated in non-small cell lung carcinoma or breast cancer stem cells | Required for normal stem cells proliferation. Upregulated in mouse neural stem cells and pluripotent cells, in particular ACC and FASN activity. |
| ACC | Carboxylate acetyl-CoA into malonyl-CoA | Upregulated in the breast, gastric, and lung cancers | Elevated in IPSCs | ||
| FASN | De novo lipogenesis | Elevated in liver, prostate, breast, ovarian, endometrial and pancreatic cancers | Overexpressed in IPSCs, NSPCs, GSCs | ||
| SCD | Catalyzes the formation of MUFAs | Higher than non-cancer adjacent tissues | Elevated in the lung, ovarian, breast, and glioblastoma cancer stem cells. SCD-dependent MUFAs could directly regulate CSCs stemness | ||
| SREBP1 | The major transcriptional regulator of lipogenesis | Promotes invasion and migration in breast cancer and colorectal cancer | Regulates stemness through lipogenesis and MUFAs formation by inducing SCD expression | ||
| Mevalonate pathway | HMG-CoAR | The rate-limiting enzyme in the MVA pathway and the popular cholesterol synthesis lowering agents | Integral to tumor growth and progression | Essential for correct membrane anchoring of Rho GTPases which maintains stemness. | Cholesterol biosynthesis mediated by mevalonate pathway is required for NSPC self-renewal and maintenance. |
| FAO | CPT family | The rate-controlling enzyme in FAO | Upregulated in less glycolytic cancer types, such as prostate adenocarcinoma and diffuse large B-cell lymphoma | Fuels multiple CSCs, such as KRAS-mutant lung cancer and MYC-driven triple-negative | Various normal stem cells rely on FAO, such as hematopoietic stem cells, neural stem cells, intestinal stem cells and skeletal muscle stem cells. |
CSCs, cancer stem cells; ACLY, ATP citrate lyase; ACC, acetyl-CoA carboxylase; FASN, FA synthase; SCD, stearoyl-CoA desaturase 1; SREBP1, sterol regulatory element binding protein 1; HMG-CoAR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; MVA, mevalonate; CPT family, carnitine palmitoyltransferase family; FAO, fatty acid; FAO, FA oxidation; IPSCs, induced pluripotent stem cells; NSPCs, neural stem and progenitor cells; GSCs, glioma stem-like cells MUFA, monounsaturated FAs; KRAS, V-Ki-ras2 Κirsten rat sarcoma viral oncogene homolog.