Nutrient Acquisition Strategies of Mammalian Cells

Overview

Journal Nature

Specialty Science

Date 2017 Jun 9

PMID 28593971

Citations 188

Authors

Wilhelm Palm

Craig B Thompson

Affiliations

Soon will be listed here.

Abstract

Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

Citing Articles

Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses.

Lesbats J, Brillac A, Reisz J, Mukherjee P, Lhuissier C, Fernandez-Monreal M Nature. 2025; .

PMID: 40011782 DOI: 10.1038/s41586-025-08629-4.

Understanding cellular proliferation activity in breast cancer using multi-compartment model of transverse relaxation time mapping on 3T MRI.

Nkonde K, Cheung S, Senn N, He J Front Oncol. 2025; 15:1482112.

PMID: 39949748 PMC: 11821498. DOI: 10.3389/fonc.2025.1482112.

Coordination between ESCRT function and Rab conversion during endosome maturation.

Ott D, Desai S, Solinger J, Kaech A, Spang A EMBO J. 2025; .

PMID: 39910226 DOI: 10.1038/s44318-025-00367-7.

Implantation of engineered adipocytes suppresses tumor progression in cancer models.

Nguyen H, An K, Ito Y, Kharbikar B, Sheng R, Paredes B Nat Biotechnol. 2025; .

PMID: 39905264 DOI: 10.1038/s41587-024-02551-2.

A Review on the Role of Human Solute Carriers Transporters in Cancer.

Hossen M, Islam M, Yasin M, Ibrahim M, Das A Health Sci Rep. 2025; 8(1):e70343.

PMID: 39807482 PMC: 11725534. DOI: 10.1002/hsr2.70343.

References

Krajcovic M, Krishna S, Akkari L, Joyce J, Overholtzer M . mTOR regulates phagosome and entotic vacuole fission. Mol Biol Cell. 2013; 24(23):3736-45. PMC: 3842999. DOI: 10.1091/mbc.E13-07-0408. View

BAILEY J . LIPID METABOLISM IN CULTURED CELLS. V. COMPARATIVE LIPID NUTRITION IN SERUM AND IN LIPID-FREE CHEMICALLY DEFINED MEDIUM. Proc Soc Exp Biol Med. 1964; 115:747-50. DOI: 10.3181/00379727-115-29026. View

Hu H, Juvekar A, Lyssiotis C, Lien E, Albeck J, Oh D . Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton. Cell. 2016; 164(3):433-46. PMC: 4898774. DOI: 10.1016/j.cell.2015.12.042. View

Caro P, Kishan A, Norberg E, Stanley I, Chapuy B, Ficarro S . Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell. 2012; 22(4):547-60. PMC: 3479446. DOI: 10.1016/j.ccr.2012.08.014. View

Semenza G, Jiang B, Leung S, Passantino R, Concordet J, Maire P . Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem. 1996; 271(51):32529-37. DOI: 10.1074/jbc.271.51.32529. View

Barnes K, Ingram J, Porras O, Barros L, Hudson E, Fryer L . Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK). J Cell Sci. 2002; 115(Pt 11):2433-42. DOI: 10.1242/jcs.115.11.2433. View

Tardito S, Oudin A, Ahmed S, Fack F, Keunen O, Zheng L . Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat Cell Biol. 2015; 17(12):1556-68. PMC: 4663685. DOI: 10.1038/ncb3272. View

Das S, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B . Adipose triglyceride lipase contributes to cancer-associated cachexia. Science. 2011; 333(6039):233-8. DOI: 10.1126/science.1198973. View

Fan J, Kamphorst J, Mathew R, Chung M, White E, Shlomi T . Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol. 2013; 9:712. PMC: 3882799. DOI: 10.1038/msb.2013.65. View

10.

Porstmann T, Santos C, Griffiths B, Cully M, Wu M, Leevers S . SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 2008; 8(3):224-36. PMC: 2593919. DOI: 10.1016/j.cmet.2008.07.007. View

11.

Palm W, Park Y, Wright K, Pavlova N, Tuveson D, Thompson C . The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1. Cell. 2015; 162(2):259-270. PMC: 4506698. DOI: 10.1016/j.cell.2015.06.017. View

12.

Kamphorst J, Nofal M, Commisso C, Hackett S, Lu W, Grabocka E . Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 2015; 75(3):544-53. PMC: 4316379. DOI: 10.1158/0008-5472.CAN-14-2211. View

13.

Lum J, Bauer D, Kong M, Harris M, Li C, Lindsten T . Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 2005; 120(2):237-48. DOI: 10.1016/j.cell.2004.11.046. View

14.

Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y . Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol. 2007; 178(1):93-105. PMC: 2064426. DOI: 10.1083/jcb.200703099. View

15.

Roczniak-Ferguson A, Petit C, Froehlich F, Qian S, Ky J, Angarola B . The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012; 5(228):ra42. PMC: 3437338. DOI: 10.1126/scisignal.2002790. View

16.

Cairns R, Harris I, Mak T . Regulation of cancer cell metabolism. Nat Rev Cancer. 2011; 11(2):85-95. DOI: 10.1038/nrc2981. View

17.

Chaudhury C, Mehnaz S, Robinson J, Hayton W, Pearl D, Roopenian D . The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med. 2003; 197(3):315-22. PMC: 2193842. DOI: 10.1084/jem.20021829. View

18.

Settembre C, Zoncu R, Medina D, Vetrini F, Erdin S, Erdin S . A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012; 31(5):1095-108. PMC: 3298007. DOI: 10.1038/emboj.2012.32. View

19.

Mayers J, Wu C, Clish C, Kraft P, Torrence M, Fiske B . Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014; 20(10):1193-1198. PMC: 4191991. DOI: 10.1038/nm.3686. View

20.

Grahame Hardie D, Ross F, Hawley S . AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012; 13(4):251-62. PMC: 5726489. DOI: 10.1038/nrm3311. View