Table 1 TGF-β-dependent glucose metabolic reprogramming and ROS regulation of cells in cancer
From: TGF-β signaling in the tumor metabolic microenvironment and targeted therapies
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 | |
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 | ||
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 | ||
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 | |
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] |