Table 1 Regulation of lipid metabolism under metabolic stress
From: Lipid metabolism in cancer cells under metabolic stress
Stress | Cancer type | Observed effects on lipid metabolism | Reference |
|---|---|---|---|
H | Breast | FASN expression upregulated via activation of Akt and SREBP-1 | |
H | Liver, prostate | Expression of markers of FA synthesis (FASN), FA desaturation (SCD-1) and TG synthesis (LIPIN1) upregulated; expression of markers of FA β-oxidation (ACADM and ACADL) and FA uptake (FABP7) downregulated; cellular TG levels increased | |
H | Liver | FASN expression downregulated only in high-density cell cultures, where hypoxia induced cytotoxic effects; FASN expression unaffected in low-density cell cultures | |
H | Brain | Expression of markers of FA synthesis (FASN, ACACA and ACACB) and mevalonate synthesis (HMGCR) downregulated; expression of markers of FA desaturation (SCD-1) and FA uptake (FABP3 and 7) upregulated | |
H | Colorectal | Expression of FA synthesis (FASN and ACACA) markers either unaffected or downregulated; expression of FA desaturation (SCD-1) markers upregulated | |
H | Liver, breast, prostate | Under hypoxia, acetate also functions as an epigenetic metabolite that enhances H3 acetylation levels in FASN and ACACA promoter regions, which upregulates FASN and ACACA expression, and increases FA synthesis | |
H | Breast, brain | Cancer cells accumulated lipid droplets under hypoxia through FA uptake (via upregulated FABP3/7), while de novo FA synthesis was repressed. Expression of perilipin 2 (a protein in lipid droplet membranes) was also upregulated. Cellular TG levels increased and TG profiles were differentially affected in different cancer cell lines | |
H | Breast, cervical, lung | Cancer cells showed increased FA [particularly of MUFA (C18:1)] uptake. Glutamine was the primary carbon source for synthesis of acetyl-CoA | |
H | Renal, colorectal | Intracellular lipolysis suppressed due to inhibition of PNPLA2 by HIG2, causing increased TG levels in hypoxic cells | |
H | Breast, cervical, lung | Cancer cells mainly reliant on glutamine and acetate for the synthesis of acetyl-CoA | |
H | Lung, breast, skin, colorectal | Under hypoxic conditions, reductive carboxylation of glutamine-derived α-ketoglutarate (α-KG) helps in supplying citrate for de novo lipogenesis. This pathway uses mitochondrial and cytosolic isoforms of isocitrate dehydrogenase | |
H | Liver, cervical, bronchial smooth muscle | Hypoxia caused TG accumulation by HIF-1-mediated stimulation of LIPIN1 expression | |
H | Prostate | Hypoxia-induced TG accumulation in extracellular vesicles (EVs) released from prostate cancer cells; upregulated expression of markers for FA synthesis (ACLY, FASN and ACACA) and FA desaturation (SCD-1); phospholipid and TG profiles both altered in cells and EVs; saturation index of membrane phospholipids increased | |
H | Cervical | Phosphatidylcholine profiles and the level of individual species were altered; relative abundance of phospholipid species with acyl chains containing ≥3 double bonds not significantly different from those containing <3 double bonds | |
H | Leukaemia, colon, lung | Cancer cells maintain lipid class homoeostasis under hypoxic stress. The levels of individual lipid moieties alter under hypoxia, but the robust averages of the broader lipid class remain unchanged | |
H | Ovarian | FABP4 expression was increased | |
H | Clear cell renal cell carcinoma | Carnitine palmitoyltransferase 1A expression is repressed, reducing FA transport into the mitochondria, and forcing FAs to accumulate lipid droplets for storage | |
LS | Breast | Cancer cells more dependent on de novo lipid synthesis | |
LS | Breast, prostate | De novo FA synthesis upregulated; cellular levels of MUFA increased | |
LS | Lung, pharynx, lung | SCD-1-mediated FA desaturation upregulated | |
LS | Leukaemia, colon, lung | In leukaemia cells neutral lipid compositions were markedly modified. Cellular level of TG subspecies decreased with increasing number of double bonds in their fatty acyl chains. Colon and lung cancer cells showed overall decrease in cholesterol ester under serum deprivation. A similar trend was observed under LS + H conditions | |
LS | Kidney | Significant reductions in TGs and cholesterol ester levels; decreases in the abundance of unsaturated TGs and a shift towards TG saturation | |
LL | Brain | Expression of SREBPs upregulated | |
LL | Prostate, lung, liver | Increased dependency on de novo FA synthesis for cell survival | |
LL | Breast, prostate | Expression of ACSS2 upregulated | |
LL | Pharynx, lung | Expression of SCD-1 upregulated | |
LL | Prostate, lung, liver, renal | Expression of markers for de novo FA synthesis (ACLY and FASN) and mevalonate synthesis (HMGCR) upregulated; expression of ACSS2 also upregulated | |
LL | Brain | Low effect on lipid droplet accumulation | |
LL | Haematopoietic | No effect on cellular cholesterol levels | |
LL | Haematopoietic | Cellular cholesterol levels unaffected; TG levels significantly elevated | |
MEM | Breast, prostate | Cancer cells primarily dependent on de novo FA synthesis; phosphatidylcholine and phosphatidylethanolamine profiles altered: the levels of phosphatidylcholines and phosphatidylethanolamines with shorter, more saturated fatty acyl chains increased | |
LS + H | Breast, prostate | Increased acetate-dependent FA synthesis | |
LL + H | Brain | Increased expression of markers for FA synthesis (FASN, ACACA, ACACB), desaturation (SCD-1) and uptake (FABP3 and 7); expression of HMGCR also upregulated | |
LS + H | Breast | Cancer cells utilised most of the acetate for synthesis of acetyl-CoA; ACSS2 mainly localised in the nucleus, where it recaptures acetate released from histone deacetylation for recycling by histone acetyl transferase | |
LL + H | Brain | Low effect on lipid droplet accumulation | |
LS + H | Kidney | Decrease in TGs harbouring unsaturated FAs and a shift towards increased TG saturation; saturation of diacyglycerols also increased |
