Table 2.
TGF-β-dependent metabolic reprogramming of lipid and amino acid in cancer
| Signaling components | TGF-β-dependent metabolic component change | Metabolic reprogramming/cell biology influenced | Cell Type | Cancer type | Experimental status | Ref. |
|---|---|---|---|---|---|---|
| Lipid | ||||||
| Cholesterol synthesis | ||||||
| NSDHL-TGF-βR2 | NSDHL promoted TGF-βR2 activation | Promoted cholesterol biosynthesis. Facilitated breast cancer cell proliferation and metastasis | Cancer cell | BC | In vitro human cell culture; Preclinical in vivo mouse model | [117] |
| NSDHL-SREBP1-TGF-β1 | NSDHL inhibited TGF-β1 production | Promoted cholesterol biosynthesis; Inhibited EMT | Cancer cell | PDAC | In vitro mouse cell culture; Preclinical in vivo mouse model | [121] |
| TGF-β-ZEB1/CtBP complex-SREBF2-TGF-βRI | ZEB1/CtBP complex Inhibited the activity of SREBF2 via bounding to its promoter | Decreased cholesterol synthesis; Increased EMT and metastasis | Cancer cell | BC | In vitro mouse cell culture; Preclinical in vivo mouse model | [123] |
| CAV-1-AKT-TGF-β1 | Downregulated CAV-1 in CAFs increased TGF-β1 through AKT activation | Increased levels of intracellular cholesterol and high metastatic behavior in CAV-1-depleted CAFs | CAF | Prostate cancer | In vitro human cell culture | [176] |
| Fatty acid synthesis | ||||||
| TGF-β1-FASN-TGF-β1 | “FASN-TGF-β1-FASN” positive regulatory loop | Increased fatty acid synthesis; Increased EMT/metastasis | Cancer cell | NSCLC | In vitro human cell culture | [126] |
| TGF-β1-ACSL5 and PPARγ | Increased ACSL5 and PPARγ | Reduced mitochondrial respiration; Increased EMT | Cancer cell | HCC | In vitro human cell culture | [98] |
| TGF-β1-p-AMPK-FASN | Activated p-AMPK and thus decreased FASN | Decreased fatty acid synthesis; Increased EMT | Cancer cell | BC | In vitro human cell culture | [127] |
| Endocytosis and lipid droplet formation | ||||||
| Acidic TMME-TGF-β2 releasement-CD36 | Acidosis increased TGF-β2 releasement and then CD36 | Increased fatty acid uptake and formation of lipid droplet; Enhanced anoikis resistance and cancer cell invasiveness | Cancer cell | Uterus and colon cancer | In vitro human cell culture | [131] |
| Fatty acid oxidation | ||||||
| TGF-β1-p-AMPK-CPT1 and CD36 | Activated p-AMPK and thus increased CPT1 and CD36 | Enhanced fatty acid oxidation pathway; Increased EMT | Cancer cell | BC | In vitro human cell culture | [127] |
| TGF-β-TGF-βRI | TGF-βRI was observed to be upregulated | Increased β-oxidation of long-chain fatty acids. Promoted TGF-β-induced EMT | Cancer cell | HCC | In vitro human cell culture | [270] |
| Amino acid | ||||||
| TGF-β-P4HA3 | Induced the expression of P4HA3 | Increased the levels of Asp, Glu, and Lys | Cancer cell | NSCLC | In vitro human cell culture; Preclinical in vivo mouse model | [137] |
| TGF-β-SLC7A5 and GLS1 | upregulated Gln transporter SLC7A5 and GLS1 | Enhanced Gln anaplerosis | Cancer cell | HCC | In vitro human cell culture | [98] |
NSDHL NAD(P)H steroid dehydrogenase-like protein; SREBF2 sterol regulatory element-binding transcription factor 2; ZEB1 zinc finger E-box-binding homeobox 1; CtBP C-terminal-binding protein; CAV-1 caveolin-1; CAFs cancer associated fibroblasts; FASN fatty acid synthase; ACSL5 acyl CoA synthetase 5; PPARγ peroxisome proliferator-activated receptor gamma; p-AMPK phosphorylated AMP-activated protein kinase; ERK extracellular signal-regulated kinase; LDs lipid droplets; CPT1 carnitine palmityl transferase 1; P4HA3 prolyl 4-hydroxylase subunit alpha 3; SLC7A5 solute carrier family 7 member 5; BC breast cancer; PDAC pancreatic ductal adenocarcinoma; NSCLC non-small cell lung cancer; and HCC hepatocellular carcinoma