Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Dec 23;10(1):3.
doi: 10.3390/cancers10010003.

Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

Yoshiaki Sunami  1 , Artur Rebelo  2 , Jörg Kleeff  3   4
Affiliations
Review

Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

Yoshiaki Sunami et al. Cancers (Basel). .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer by 2030, and the overall 5-year survival rate is currently less than 7%. Cancer cells frequently exhibit reprogramming of their metabolic activity. It is increasingly recognized that aberrant de novo lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of various cancers, including pancreatic cancer. In this review, the current knowledge about lipid metabolism and lipid droplets in pancreatic cancer is discussed. In the first part, molecular mechanisms of lipid metabolism and roles of enzymes involved in lipid metabolism which are relevant for pancreatic cancer research are presented. Further, preclinical studies and clinical trials with drugs/inhibitors targeting cancer metabolic systems in cancer are summarized. An increase of our knowledge in lipid metabolism in pancreatic cancer cells and in tumor stroma is important for developing novel strategies of future individualized therapies of pancreatic cancer.

Keywords: lipid droplets; lipid metabolism; pancreatic ductal adenocarcinoma; pancreatic stellate cells; reprogramming in lipid metabolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Central pathway for fatty acid and cholesterol synthesis (ACC: Acetyl-CoA carboxylase; ACLY: ATP-citrate lyase; AMPK: AMP-activated protein kinase; ER: endoplasmic reticulum; FA: fatty acid; FASN: fatty acid synthase; HMG: 3-hydroxy-3-methylglutaryl-coenzyme A; LKB1: liver kinase B1; LDLR: low-density lipoprotein receptor; SCD: ∆9-stearoyl-CoA desaturase; SREBP: sterol regulatory element-binding protein; TCA cycle: tricarboxylic acid cycle).
Figure 2
Figure 2
Canonical as well as non-canonical glutaminolysis pathways, and acetate pathway for supporting lipid metabolism in cancer (ACSS: acyl-CoA synthetase short chain family member; ALDH: Aldehyde dehydrogenase; CiC: citrate carrier; GLS: glutaminase; GLUD: glutamate dehydrogenase; GOT: aspartate transaminase; α-KG: α-ketoglutarate; IDH: isocitrate dehydrogenase; MCT: monocarboxylate transporter; MDH: malate dehydrogenase; ME: malate enzyme; SLC: solute carrier; TCA: tricarboxylic acid cycle).
Figure 3
Figure 3
Overview of inhibitors for targeting lipid metabolism in cancers (ACAT: acyl-CoA cholesterol acyltransferase; ACC: Acetyl-CoA carboxylase; ACLY: ATP-citrate lyase; ACSS: acyl-CoA synthetase short chain family member; AMPK: AMP-activated protein kinase; ALDH: Aldehyde dehydrogenase; CiC: citrate carrier; ER: endoplasmic reticulum; FA: fatty acid; FASN: fatty acid synthase; GLS: glutaminase; GLUD: glutamate dehydrogenase; GOT: aspartate transaminase; HIF: hypoxia inducible factor; HMG: 3-hydroxy-3-methylglutaryl-coenzyme A; IDH: isocitrate dehydrogenase; α-KG: α-ketoglutarate; LKB1: liver kinase B1; LDLR: low-density lipoprotein receptor; MCT: monocarboxylate transporter; MDH: malate dehydrogenase; ME: malate enzyme; SCD: ∆9-stearoyl-CoA desaturase; SLC: solute carrier; SREBP: sterol regulatory element-binding protein; TCA: tricarboxylic acid cycle).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kleeff J., Korc M., Apte M., La Vecchia C., Johnson C.D., Biankin A.V., Neale R.E., Tempero M., Tuveson D.A., Hruban R.H., et al. Pancreatic cancer. Nat. Rev. Dis. Primers. 2016;2:16022. doi: 10.1038/nrdp.2016.22. - DOI - PubMed
    1. Rahib L., Smith B.D., Aizenberg R., Rosenzweig A.B., Fleshman J.M., Matrisian L.M. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–2921. doi: 10.1158/0008-5472.CAN-14-0155. - DOI - PubMed
    1. Neoptolemos J.P., Palmer D.H., Ghaneh P., Psarelli E.E., Valle J.W., Halloran C.M., Faluyi O., O’Reilly D.A., Cunningham D., Wadsley J., et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389:1011–1024. doi: 10.1016/S0140-6736(16)32409-6. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. Hallmark of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Philip B., Roland C.L., Daniluk J., Liu Y., Chatterjee D., Gomez S.B., Ji B., Huang H., Wang H., Fleming J.B., et al. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice. Gastroenterology. 2013;145:1449–1458. doi: 10.1053/j.gastro.2013.08.018. - DOI - PMC - PubMed