Macropinocytosis and Cancer: From Tumor Stress to Signaling Pathways.
Cancer malignancy
Cell metabolism
Macropinocytosis
Nutrient scarcity
Nutrient uptake
Stress stimuli
Journal
Sub-cellular biochemistry
ISSN: 0306-0225
Titre abrégé: Subcell Biochem
Pays: United States
ID NLM: 0316571
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
5
4
2022
pubmed:
6
4
2022
medline:
7
4
2022
Statut:
ppublish
Résumé
Macropinocytosis is an evolutionarily conserved endocytic pathway that mediates the nonselective acquisition of extracellular material via large endocytic vesicles known as macropinosomes. In addition to other functions, this uptake pathway supports cancer cell metabolism through the uptake of nutrients. Cells harboring oncogene or tumor suppressor mutations are known to display heightened macropinocytosis, which confers to the cancer cells the ability to survive and proliferate despite the nutrient-scarce conditions of the tumor microenvironment. Thus, macropinocytosis is associated with cancer malignancy. Macropinocytic uptake can be induced in cancer cells by different stress stimuli, acting as an adaptive mechanism for the cells to resist stresses in the tumor milieu. Here, we review the cellular stresses that are known to promote macropinocytosis, as well as the underlying molecular mechanisms that drive this process.
Identifiants
pubmed: 35378701
doi: 10.1007/978-3-030-94004-1_2
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
15-40Subventions
Organisme : NCI NIH HHS
ID : R01 CA207189
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA254806
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
Ackerman D et al (2018) Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep 24(10):2596–2605 e5
pubmed: 30184495
pmcid: 6137821
Agani F, Jiang BH (2013) Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTOR pathway in cancer. Curr Cancer Drug Targets 13(3):245–251
pubmed: 23297826
Anthony JC et al (2001) Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 131(3):856S–860S
pubmed: 11238774
Araki N, Johnson MT, Swanson JA (1996) A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol 135(5):1249–1260
pubmed: 8947549
Araki N et al (2007) Phosphoinositide metabolism during membrane ruffling and macropinosome formation in EGF-stimulated A431 cells. Exp Cell Res 313(7):1496–1507
pubmed: 17368443
Ard R et al (2015) Regulation of macropinocytosis by diacylglycerol kinase zeta. PLoS One 10(12):e0144942
pubmed: 26701304
pmcid: 4689489
Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495
pubmed: 15734681
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313
pubmed: 17237347
Bloomfield G, Kay RR (2016) Uses and abuses of macropinocytosis. J Cell Sci 129(14):2697–2705
pubmed: 27352861
Bohdanowicz M et al (2013) Phosphatidic acid is required for the constitutive ruffling and macropinocytosis of phagocytes. Mol Biol Cell 24(11):1700–1712, S1-7
pubmed: 23576545
pmcid: 3667723
Bryant DM et al (2007) EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin. J Cell Sci 120(Pt 10):1818–1828
pubmed: 17502486
Canton J et al (2016) Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages. Nat Commun 7:11284
pubmed: 27050483
pmcid: 4823870
Cao Y et al (2019) Extracellular and macropinocytosis internalized ATP work together to induce epithelial-mesenchymal transition and other early metastatic activities in lung cancer. Cancer Cell Int 19:254
pubmed: 31582910
pmcid: 6771108
Cepeda EB et al (2015) Mechanisms regulating cell membrane localization of the chemokine receptor CXCR4 in human hepatocarcinoma cells. Biochim Biophys Acta 1853(5):1205–1218
pubmed: 25704914
Chen Q et al (2018) Rewiring of glutamine metabolism is a bioenergetic adaptation of human cells with mitochondrial DNA mutations. Cell Metab 27(5):1007–1025 e5
pubmed: 29657030
pmcid: 5932217
Choi YH (2018) ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells. Gen Physiol Biophys 37(2):129–140
pubmed: 29593120
Choi SH et al (2009) Lipoprotein accumulation in macrophages via toll-like receptor-4-dependent fluid phase uptake. Circ Res 104(12):1355–1363
pubmed: 19461045
pmcid: 2741301
Colavitti R, Finkel T (2005) Reactive oxygen species as mediators of cellular senescence. IUBMB Life 57(4–5):277–281
pubmed: 16036611
Commisso C, Debnath J (2018) Macropinocytosis fuels prostate cancer. Cancer Discov 8(7):800–802
pubmed: 29967075
Commisso C et al (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497(7451):633–637
pubmed: 23665962
pmcid: 3810415
Cybulski N, Hall MN (2009) TOR complex 2: a signaling pathway of its own. Trends Biochem Sci 34(12):620–627
pubmed: 19875293
Davidson SM, Vander Heiden MG (2017) Critical functions of the lysosome in cancer biology. Annu Rev Pharmacol Toxicol 57:481–507
pubmed: 27732799
Davidson SM et al (2017) Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat Med 23(2):235–241
pubmed: 28024083
Daye D, Wellen KE (2012) Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol 23(4):362–369
pubmed: 22349059
Dharmawardhane S et al (2000) Regulation of macropinocytosis by p21-activated kinase-1. Mol Biol Cell 11(10):3341–3352
pubmed: 11029040
pmcid: 14996
Djordjevic T et al (2005) The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells. Free Radic Biol Med 38(5):616–630
pubmed: 15683718
Donaldson JG, Porat-Shliom N, Cohen LA (2009) Clathrin-independent endocytosis: a unique platform for cell signaling and PM remodeling. Cell Signal 21(1):1–6
pubmed: 18647649
Farnsworth RH et al (2014) Vascular remodeling in cancer. Oncogene 33(27):3496–3505
pubmed: 23912450
Fruman DA, Rommel C (2014) PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 13(2):140–156
pubmed: 24481312
pmcid: 3994981
Fujii M et al (2013) Dissecting the roles of Rac1 activation and deactivation in macropinocytosis using microscopic photo-manipulation. Sci Rep 3:2385
pubmed: 23924974
pmcid: 3737501
Garcia D, Shaw RJ (2017) AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell 66(6):789–800
pubmed: 28622524
pmcid: 5553560
Ghoshal P et al (2017) Nox2-mediated PI3K and cofilin activation confers alternate redox control of macrophage pinocytosis. Antioxid Redox Signal 26(16):902–916
pubmed: 27488058
pmcid: 5455614
Gu Z et al (2011) Integrins traffic rapidly via circular dorsal ruffles and macropinocytosis during stimulated cell migration. J Cell Biol 193(1):61–70
pubmed: 21464228
pmcid: 3082178
Gullino PM, Grantham FH, Courtney AH (1967) Glucose consumption by transplanted tumors in vivo. Cancer Res 27(6):1031–1040
pubmed: 4290857
Gwinn DM et al (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30(2):214–226
pubmed: 18439900
pmcid: 2674027
Hawkins KE et al (2016) NRF2 orchestrates the metabolic shift during induced pluripotent stem cell reprogramming. Cell Rep 14(8):1883–1891
pubmed: 26904936
pmcid: 4785773
Hess D, Chisholm JW, Igal RA (2010) Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS One 5(6):e11394
pubmed: 20613975
pmcid: 2894866
Hinchy EC et al (2018) Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem 293(44):17208–17217
pubmed: 30232152
pmcid: 6222118
Hobbs GA, Der CJ, Rossman KL (2016) RAS isoforms and mutations in cancer at a glance. J Cell Sci 129(7):1287–1292
pubmed: 26985062
pmcid: 4869631
Hobbs GA et al (2020) Atypical KRAS(G12R) mutant is impaired in PI3K signaling and macropinocytosis in pancreatic cancer. Cancer Discov 10(1):104–123
pubmed: 31649109
Hodakoski C et al (2019) Rac-mediated macropinocytosis of extracellular protein promotes glucose independence in non-small cell lung cancer. Cancers (Basel) 11(1)
Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115(5):577–590
pubmed: 14651849
Jayashankar V, Edinger AL (2020) Macropinocytosis confers resistance to therapies targeting cancer anabolism. Nat Commun 11(1):1121
pubmed: 32111826
pmcid: 7048872
Jewell JL, Guan KL (2013) Nutrient signaling to mTOR and cell growth. Trends Biochem Sci 38(5):233–242
pubmed: 23465396
pmcid: 3634910
Kamphorst JJ et al (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A 110(22):8882–8887
pubmed: 23671091
pmcid: 3670379
Kamphorst JJ et al (2015) Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res 75(3):544–553
pubmed: 25644265
pmcid: 4316379
Karasic TB et al (2019) Effect of gemcitabine and nab-paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: a phase 2 randomized clinical trial. JAMA Oncol 5(7):993–998
pubmed: 31120501
pmcid: 6547080
Karna E et al (2020) Proline-dependent regulation of collagen metabolism. Cell Mol Life Sci 77(10):1911–1918
pubmed: 31740988
Karsli-Uzunbas G et al (2014) Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov 4(8):914–927
pubmed: 24875857
pmcid: 4125614
Kasahara K et al (2007) Role of Src-family kinases in formation and trafficking of macropinosomes. J Cell Physiol 211(1):220–232
pubmed: 17167779
Keith B, Johnson RS, Simon MC (2011) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12(1):9–22
pubmed: 22169972
pmcid: 3401912
Kim SM et al (2018) PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells. Cancer Discov 8(7):866–883
pubmed: 29572236
pmcid: 6030497
King B et al (2020) Yap/Taz promote the scavenging of extracellular nutrients through macropinocytosis. Genes Dev 34(19–20):1345–1358
pubmed: 32912902
pmcid: 7528706
Kondratowicz AS et al (2013) AMP-activated protein kinase is required for the macropinocytic internalization of ebolavirus. J Virol 87(2):746–755
pubmed: 23115293
pmcid: 3554099
Koong AC, Chen EY, Giaccia AJ (1994) Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54(6):1425–1430
pubmed: 8137243
Kuper A et al (2021) Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis. Cell Death Dis 12(1):82
pubmed: 33441543
pmcid: 7806930
Lee P, Chandel NS, Simon MC (2020) Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol 21(5):268–283
pubmed: 32144406
pmcid: 7222024
Lee SW et al (2019) EGFR-Pak signaling selectively regulates glutamine deprivation-induced macropinocytosis. Dev Cell 50(3):381–392 e5
pubmed: 31257175
pmcid: 6684838
Li H et al (2019) Role of Nrf2 in the antioxidation and oxidative stress induced developmental toxicity of honokiol in zebrafish. Toxicol Appl Pharmacol 373:48–61
pubmed: 31022495
Liberali P et al (2008) The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS. EMBO J 27(7):970–981
pubmed: 18354494
pmcid: 2323256
Liu Z, Roche PA (2015) Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells. Front Physiol 6:1
pubmed: 25688210
pmcid: 4311620
Liu W et al (2012) Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci U S A 109(23):8983–8988
pubmed: 22615405
pmcid: 3384197
Luo W et al (2011) Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145(5):732–744
pubmed: 21620138
pmcid: 3130564
Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426
pubmed: 23294312
pmcid: 4680839
Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10(5):307–318
pubmed: 19339977
Melander MC et al (2015) The collagen receptor uPARAP/Endo180 in tissue degradation and cancer (Review). Int J Oncol 47(4):1177–1188
pubmed: 26316068
pmcid: 4583827
Mercer J, Helenius A (2009) Virus entry by macropinocytosis. Nat Cell Biol 11(5):510–520
pubmed: 19404330
Merlot AM, Kalinowski DS, Richardson DR (2014) Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol 5:299
pubmed: 25161624
pmcid: 4129365
Michalopoulou E et al (2020) Macropinocytosis renders a subset of pancreatic tumor cells resistant to mTOR inhibition. Cell Rep 30(8):2729–2742 e4
pubmed: 32101748
pmcid: 7043007
Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147(4):728–741
pubmed: 22078875
pmcid: 22078875
Moser TS et al (2010) A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics. PLoS Pathog 6(6):e1000954
pubmed: 20585561
pmcid: 2887478
Muz B et al (2015) The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl) 3:83–92
Nakase I et al (2015) Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes. Sci Rep 5:10300
pubmed: 26036864
pmcid: 4453128
Navale AM, Paranjape AN (2016) Glucose transporters: physiological and pathological roles. Biophys Rev 8(1):5–9
pubmed: 28510148
pmcid: 5425736
Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284(20):13291–13295
pubmed: 19182219
pmcid: 2679427
Nofal M et al (2017) mTOR inhibition restores amino acid balance in cells dependent on catabolism of extracellular protein. Mol Cell 67(6):936–946 e5
pubmed: 28918901
pmcid: 5612669
Oh ET et al (2016) NQO1 inhibits proteasome-mediated degradation of HIF-1alpha. Nat Commun 7:13593
pubmed: 27966538
pmcid: 5171868
Olivares O et al (2017) Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun 8:16031
pubmed: 28685754
pmcid: 5504351
Onodera J, Ohsumi Y (2005) Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation. J Biol Chem 280(36):31582–31586
pubmed: 16027116
Palm W (2019) Metabolic functions of macropinocytosis. Philos Trans R Soc Lond B Biol Sci 374(1765):20180285
pubmed: 30967008
Palm W et al (2015) The utilization of extracellular proteins as nutrients is suppressed by mTORC1. Cell 162(2):259–270
pubmed: 26144316
pmcid: 4506698
Palm W et al (2017) Critical role for PI3-kinase in regulating the use of proteins as an amino acid source. Proc Natl Acad Sci U S A 114(41):E8628–E8636
pubmed: 28973876
pmcid: 5642723
Pizzimenti S et al (2010) The “two-faced” effects of reactive oxygen species and the lipid peroxidation product 4-hydroxynonenal in the hallmarks of cancer. Cancers (Basel) 2(2):338–363
Qian Y et al (2014) Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells. Cancer Lett 351(2):242–251
pubmed: 24973521
Racoosin EL, Swanson JA (1989) Macrophage colony-stimulating factor (rM-CSF) stimulates pinocytosis in bone marrow-derived macrophages. J Exp Med 170(5):1635–1648
pubmed: 2681516
Racoosin EL, Swanson JA (1993) Macropinosome maturation and fusion with tubular lysosomes in macrophages. J Cell Biol 121(5):1011–1020
pubmed: 8099075
Recouvreux MV, Commisso C (2017) Macropinocytosis: a metabolic adaptation to nutrient stress in cancer. Front Endocrinol (Lausanne) 8:261
Redelman-Sidi G et al (2018) The canonical Wnt pathway drives macropinocytosis in cancer. Cancer Res 78(16):4658–4670
pubmed: 29871936
pmcid: 6226250
Ridley AJ et al (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70(3):401–410
pubmed: 1643658
Sarbassov DD et al (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307(5712):1098–1101
pubmed: 15718470
Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 169(2):361–371
pubmed: 28388417
Schmees C et al (2012) Macropinocytosis of the PDGF beta-receptor promotes fibroblast transformation by H-RasG12V. Mol Biol Cell 23(13):2571–2582
pubmed: 22573884
pmcid: 3386220
Schrader M, Fahimi HD (2004) Mammalian peroxisomes and reactive oxygen species. Histochem Cell Biol 122(4):383–393
pubmed: 15241609
Seguin L et al (2017) Galectin-3, a druggable vulnerability for KRAS-addicted cancers. Cancer Discov 7(12):1464–1479
pubmed: 28893801
pmcid: 5718959
Semenza GL (2013) HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 123(9):3664–3671
pubmed: 23999440
pmcid: 3754249
Shaw RJ (2009) LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf) 196(1):65–80
Singla B et al (2018) PKCdelta-mediated Nox2 activation promotes fluid-phase pinocytosis of antigens by immature dendritic cells. Front Immunol 9:537
pubmed: 29632528
pmcid: 5879126
Su H et al (2021) Cancer cells escape autophagy inhibition via NRF2-induced macropinocytosis. Cancer Cell
Swanson JA (2008) Shaping cups into phagosomes and macropinosomes. Nat Rev Mol Cell Biol 9(8):639–649
pubmed: 18612320
pmcid: 2851551
Tao S et al (2019) Correction: oncogenic KRAS confers chemoresistance by upregulating NRF2. Cancer Res 79(5):1015
pubmed: 30824678
Thompson CB (2011) Rethinking the regulation of cellular metabolism. Cold Spring Harb Symp Quant Biol 76:23–29
pubmed: 22429931
Topham MK, Prescott SM (2001) Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism. J Cell Biol 152(6):1135–1143
pubmed: 11257115
pmcid: 2199204
Toth RK, Warfel NA, Bedfellows S (2017) Nuclear factor, erythroid 2-like 2 (Nrf2) and hypoxia-inducible factor 1 (HIF-1) in tumor hypoxia. Antioxidants (Basel) 6(2)
Urasaki Y, Heath L, Xu CW (2012) Coupling of glucose deprivation with impaired histone H2B monoubiquitination in tumors. PLoS One 7(5):e36775
pubmed: 22615809
pmcid: 3353945
Veithen A et al (1996) v-Src induces constitutive macropinocytosis in rat fibroblasts. J Cell Sci 109(Pt 8):2005–2012
pubmed: 8856496
Wang X, Proud CG (2006) The mTOR pathway in the control of protein synthesis. Physiology (Bethesda) 21:362–369
Waters AM, Der CJ (2018) KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb Perspect Med 8(9)
Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17(11):1359–1370
pubmed: 22064426
Wennstrom S et al (1994) Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling. Curr Biol 4(5):385–393
pubmed: 7922352
West MA, Bretscher MS, Watts C (1989) Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J Cell Biol 109(6 Pt 1):2731–2739
pubmed: 2556406
Westphalen CB, Olive KP (2012) Genetically engineered mouse models of pancreatic cancer. Cancer J 18(6):502–510
pubmed: 23187836
pmcid: 3594661
Yoshida S et al (2015) Growth factor signaling to mTORC1 by amino acid-laden macropinosomes. J Cell Biol 211(1):159–172
pubmed: 26438830
pmcid: 4602043
Yoshida S et al (2018) Macropinocytosis, mTORC1 and cellular growth control. Cell Mol Life Sci 75(7):1227–1239
pubmed: 29119228
Yue S et al (2014) Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab 19(3):393–406
pubmed: 24606897
pmcid: 3969850
Zhang Y et al (2021) Macropinocytosis in cancer-associated fibroblasts is dependent on CaMKK2/ARHGEF2 signaling and functions to support tumor and stromal cell fitness. Cancer Discov