Table 1.
TGF-β-dependent glucose metabolic reprogramming and ROS regulation of cells in cancer
| Signaling components | TGF-β-dependent metabolic component change | Metabolic reprogramming/cell biology influenced | Cancer type | Experimental status | Ref. | |
|---|---|---|---|---|---|---|
| Cancer cell | ||||||
| Glycolysis | TGF-β1-GLUT1 | TGF-β enhanced the expression of GLUT1 | Increased glucose uptake, induced EMT | BC, pancreatic carcinoma | In vitro human cell culture | [76–78] |
| ANGPTL2-α5β1-TGF-β-ZEB1-GLUT3 | ANGPTL2 increased GLUT3 expression by TGF-β signaling activation | Elevated glycolysis, promoted metastasis and EMT | NSCLC | In vitro human cell culture | [266] | |
| TGF-β1-HK2 | TGF-β1 increased mRNA expression of HK2 | Increased glycolysis; Promoted proliferation and metastasis | Neuroblastoma and gallbladder cancer | In vivo mouse model | [84] | |
| TGF-β1-PFKFB3 | TGF-β1 elevated PFKFB3 | Increased glucose uptake, glycolytic flux, and lactate production; Promoted invasion | Glioma and pancreatic carcinoma | In vitro human cell culture | [84, 87] | |
| TGF-β-TGFIF/PKM2 | TGFIF and PKM2 were increased under TGF-β1 stimulation | Promote Warburg effect and promoted EMT | Colorectal cancer, lung carcinoma | In vitro human cell culture | [89, 90] | |
| TGF-β-mTOR-p70s6k-PKM2 | TGF-β1 increased the expression of PKM2 | Influenced glycolysis and Warburg effect, induced EMT | Cervical cancer | In vitro human cell culture | [267] | |
| TCA cycle | SDHB-TGF-β-SMAD3/SMAD4-SNAL1 | SDHB deficiency activated TGF-β signaling | Induced mitochondrial enzyme SDH dysfunction; Increased invasion and migration via EMT | Colorectal cancer | In vitro human cell culture | [96] |
| Pentose phosphate pathway | TGF-β1-FOXM1-HMGA1-G6PD-TGF-β1 | Increased the expression of G6PD via TGF-β signaling activation | Enhanced PPP and thus increased cisplatin resistance | NSCLC | In vitro human cell culture | [101] |
| Glycogen Synthesis | TGF-β1-LEFTY2-SGLT1 and GYS1 | inhibited LEFTY2 expression, and decreased SGLT1 and GYS1 | Negated glycogen formation | Endometrial cancer | In vitro human cell culture | [102] |
| GSK-3β-TGF-β/SMAD3 signaling | GSK-3β inhibited activity of SMAD3 under TGF-β stimulation | Not mentioned | HCC | In vitro human cell culture | [103] | |
| TGF-β-GSK-3β-HNF4α | Inhibited GSK-3β and then hamper the activation of tumor suppressor HNF4α | Promoted EMT | HCC | In vitro human cell culture | [104] | |
| ROS | TGF-β2-catalase-H2O2 | Reduced the amount of H2O2 by catalase overexpression | Regulated H2O2 redox balance and acquired aggressive dissemination phenotype | NSCLC | In vitro bovine and human cell culture | [268] |
| TGF-β1-ROS-ERK | Activated ERK signaling by TGF-β1-mediated ROS production | Downregulated ATP consumption, inhibited cell growth, and induced apoptosis | Colon cancer | In vitro human cell culture | [269] | |
| Fibroblast | ||||||
| Glycolysis | TGF-β-CAV-1-TGF-β activation | Downregulated CAV-1 and activated TGF-β signaling in turn | Promoted RWE, increased glycolysis and decreased OXPHOS | Skin cancer | In vitro human cell culture; in vivo mouse model | [16] |
| TGF-β1-IDH3α | Downregulated IDH3α by TGF-β1 treatment | Increased glycolysis and switched from oxidative phosphorylation to aerobic glycolysis | Melanoma | In vitro human cell culture; in vivo mouse model | [150] | |
| TCA cycle | TGF-β-PDK1 | Activated PDK1 | Decrease entry of pyruvate into the TCA cycle | Lymphoma and renal cell carcinoma | In vitro human cell culture | [169, 170] |
| NK cell | ||||||
| Glycolysis and OXPHOS | GARP-TGF-β-mTOR1-CD71 | Increased expression of GARP activated TGF-β signaling and then downregulated mTOR1 and CD71 | Reduced glycolysis and OXPHOS; Damaged effector function of NK cells | BC | In vitro human cell culture | [219] |
| Macrophage | ||||||
| OXPHOS | TGF-β ligand | May enhance OXPHOS by TGF-β signaling activation | Promoted macrophage polarization to M2-phenotype and inhibited its immune toxicity | Melanoma | In vitro mouse cell culture | [221] |
| T cell | ||||||
| OXPHOS | TGF-β-SMAD-ATP synthase-IFNγ | Inhibited ATP synthase activity | Inhibited IFNγ production and diminished T cell function | Pancreatic, lung, urothelial, and cholangiocellular cancers | In vitro human cell culture | [235] |
GLUT glucose transporter; HK2 hexokinase 2; PFKFB3 6-phosphofructo-2-kinase; TGIF2 TGF-β-induced factor homeobox 2; H3K9 histone H3 lysine 9; ANGPTL2 angiopoietin-like protein 2; ZEB1 zinc finger E-box-binding homeobox 1; PKM2 pyruvate kinase M2; TCA cycle Tricarboxylic acid cycle; OXPHOS oxidative phosphorylation; SDHB succinate dehydrogenase B subunit; SDH succinate dehydrogenase; FOXM1 forkhead box M1; HMGA1 high mobility group A; G6PD glucose-6-phosphate dehydrogenase; LEFTY2 endometrial bleeding-associated factor; GSK-3β glycogen synthase kinase 3; HNF4α hepatocyte nuclear factor 4; mtDNA mitochondrial DNA; Cyt C cytochrome c; ROS reactive oxygen species; ERK extracellular signal-regulated kinase; PCK1 phosphoenolpyruvate carboxykinase 1; CAV-1 caveolin-1; IDH3α isocitric dehydrogenase 3; PDK1 pyruvate dehydrogenase kinase 1; GARP glycoprotein A repetitions predominant; BC breast cancer; NSCLC non-small cell lung cancer; HCC hepatocellular carcinoma; and PDAC pancreatic ductal adenocarcinoma