Table 2 TGF-β-dependent metabolic reprogramming of lipid and amino acid 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 | 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] |