Skip to main content
SpringerLink
Log in

Roles for Phospholipase D1 in the Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1259))

Abstract

The lipid-modifying signal transduction enzyme phospholipase D (PLD) has been proposed to have roles in oncogenic processes for well-on 30 years, with most of the early literature focused on potential functions for PLD in the biology of the tumor cells themselves. While such roles remain under investigation, evidence has also now been generated to support additional roles for PLD, in particular PLD1, in the tumor microenvironment, including effects on neoangiogenesis, the supply of nutrients, interactions of platelets with circulating cancer cells, the response of the immune system, and exosome biology. Here, we review these lines of investigation, accompanied by a discussion of the limitations of the existing studies and some cautionary notes regarding the study and interpretation of PLD function using model systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA (1995) Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J Biol Chem 270:29640–29643

    Article  CAS  Google Scholar 

  2. Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, BarSagi D, Morris AJ, Frohman MA (1997) Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization. Curr Biol 7:191–201. https://doi.org/10.1016/S0960-9822(97)70090-3

    Article  CAS  PubMed  Google Scholar 

  3. Jenkins GM, Frohman MA (2005) Phospholipase D: a lipid centric review. Cell Mol Life Sci 62:2305–2316. https://doi.org/10.1007/s00018-005-5195-z

    Article  CAS  PubMed  Google Scholar 

  4. Gavin AL et al (2018) PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing. Nat Immunol 19:942–953. https://doi.org/10.1038/s41590-018-0179-y. PMC6105523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Frohman MA (2015) The phospholipase D superfamily as therapeutic targets. Trends Pharmacol Sci 36:137–144. https://doi.org/10.1016/j.tips.2015.01.001. PMC4355084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Choi SY, Huang P, Jenkins GM, Chan DC, Schiller J, Frohman MA (2006) A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nat Cell Biol 8:1255–1262. https://doi.org/10.1038/ncb1487

    Article  CAS  PubMed  Google Scholar 

  7. Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O (2012) Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 491:284–287. https://doi.org/10.1038/nature11509

    Article  CAS  PubMed  Google Scholar 

  8. Huang H, Gao Q, Peng X, Choi SY, Sarma K, Ren H, Morris AJ, Frohman MA (2011) piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. Develop Cell 20:376–387. https://doi.org/10.1016/j.devcel.2011.01.004. PMC3061402

    Article  CAS  Google Scholar 

  9. Tookey HL, Balls AK (1956) Plant phospholipase D. I. Studies on cottonseed and cabbage phospholipase D. J Biol Chem 218:213–224

    CAS  PubMed  Google Scholar 

  10. Kanfer JN (1980) The base exchange enzymes and phospholipase D of mammalian tissue. Can J Biochem 58:1370–1380. https://doi.org/10.1139/o80-186

    Article  CAS  PubMed  Google Scholar 

  11. Pai JK, Siegel MI, Egan RW, Billah MM (1988) Activation of phospholipase D by chemotactic peptide in HL-60 granulocytes. Biochem Biophys Res Commun 150:355–364. https://doi.org/10.1016/0006-291x(88)90528-1

    Article  CAS  PubMed  Google Scholar 

  12. Tettenborn CS, Mueller GC (1988) 12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates. Biochem Biophys Res Commun 155:249–255. https://doi.org/10.1016/s0006-291x(88)81076-3

    Article  CAS  PubMed  Google Scholar 

  13. Lopez-Barahona M, Kaplan PL, Cornet ME, Diaz-Meco MT, Larrodera P, Diaz-Laviada I, Municio AM, Moscat J (1990) Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki-ras oncogene. Possible involvement in late steps of the mitogenic cascade. J Biol Chem 265:9022–9026

    CAS  PubMed  Google Scholar 

  14. Kaszkin M, Richards J, Kinzel V (1992) Proposed role of phosphatidic acid in the extracellular control of the transition from G2 phase to mitosis exerted by epidermal growth factor in A431 cells. Cancer Res 52:5627–5634

    CAS  PubMed  Google Scholar 

  15. Zhang W, Nakashima T, Sakai N, Yamada H, Okano Y, Nozawa Y (1992) Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: possible role in mitogenic signal transduction. Neurol Res 14:397–401. https://doi.org/10.1080/01616412.1992.11740092

    Article  CAS  PubMed  Google Scholar 

  16. Martinson EA, Trilivas I, Brown JH (1990) Rapid protein kinase C-dependent activation of phospholipase D leads to delayed 1,2-diglyceride accumulation. J Biol Chem 265:22282–22287

    CAS  PubMed  Google Scholar 

  17. Brown HA, Thomas PG, Lindsley CW (2017) Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nat Rev Drug Discov 16:351–367. https://doi.org/10.1038/nrd.2016.252. PMC6040825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cho JH, Han JS (2017) Phospholipase D and its essential role in cancer. Mol Cells 40:805–813. https://doi.org/10.14348/molcells.2017.0241. PMC5712509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brown HA, Gutowski S, Moomaw CR, Slaughter C, Sternweis PC (1993) ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Cell 75:1137–1144. https://doi.org/10.1016/0092-8674(93)90323-i

    Article  CAS  PubMed  Google Scholar 

  20. Kahn RA, Yucel JK, Malhotra V (1993) ARF signaling: a potential role for phospholipase D in membrane traffic. Cell 75:1045–1048. https://doi.org/10.1016/0092-8674(93)90314-g

    Article  CAS  PubMed  Google Scholar 

  21. Ohguchi K, Banno Y, Nakashima S, Nozawa Y (1995) Activation of membrane-bound phospholipase D by protein kinase C in HL60 cells: synergistic action of a small GTP-binding protein RhoA. Biochem Biophys Res Commun 211:306–311. https://doi.org/10.1006/bbrc.1995.1811

    Article  CAS  PubMed  Google Scholar 

  22. Cross MJ, Roberts S, Ridley AJ, Hodgkin MN, Stewart A, Claesson-Welsh L, Wakelam MJ (1996) Stimulation of actin stress fibre formation mediated by activation of phospholipase D. Curr Biol 6:588–597. https://doi.org/10.1016/s0960-9822(02)00545-6

    Article  CAS  PubMed  Google Scholar 

  23. Williger BT, Ho WT, Exton JH (1999) Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells. J Biol Chem 274:735–738. https://doi.org/10.1074/jbc.274.2.735

    Article  CAS  PubMed  Google Scholar 

  24. Uchida N, Okamura S, Nagamachi Y, Yamashita S (1997) Increased phospholipase D activity in human breast cancer. J Cancer Res Clin Oncol 123:280–285. https://doi.org/10.1007/bf01208639

    Article  CAS  PubMed  Google Scholar 

  25. Joseph T, Wooden R, Bryant A, Zhong M, Lu Z, Foster DA (2001) Transformation of cells overexpressing a tyrosine kinase by phospholipase D1 and D2. Biochem Biophys Res Commun 289:1019–1024. https://doi.org/10.1006/bbrc.2001.6118

    Article  CAS  PubMed  Google Scholar 

  26. Min DS, Kwon TK, Park WS, Chang JS, Park SK, Ahn BH, Ryoo ZY, Lee YH, Lee YS, Rhie DJ, Yoon SH, Hahn SJ, Kim MS, Jo YH (2001) Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts. Carcinogenesis 22:1641–1647. https://doi.org/10.1093/carcin/22.10.1641

    Article  CAS  PubMed  Google Scholar 

  27. Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science (New York, NY) 294:1942–1945. https://doi.org/10.1126/science.1066015

    Article  CAS  Google Scholar 

  28. Zhong M, Shen Y, Zheng Y, Joseph T, Jackson D, Foster DA (2003) Phospholipase D prevents apoptosis in v-Src-transformed rat fibroblasts and MDA-MB-231 breast cancer cells. Biochem Biophys Res Commun 302:615–619. https://doi.org/10.1016/s0006-291x(03)00229-8

    Article  CAS  PubMed  Google Scholar 

  29. Toschi A, Edelstein J, Rockwell P, Ohh M, Foster DA (2008) HIF alpha expression in VHL-deficient renal cancer cells is dependent on phospholipase D. Oncogene 27:2746–2753. https://doi.org/10.1038/sj.onc.1210927

    Article  CAS  PubMed  Google Scholar 

  30. Chae YC, Kim JH, Kim KL, Kim HW, Lee HY, Heo WD, Meyer T, Suh PG, Ryu SH (2008) Phospholipase D activity regulates integrin-mediated cell spreading and migration by inducing GTP-Rac translocation to the plasma membrane. Mol Biol Cell 19:3111–3123. https://doi.org/10.1091/mbc.E07-04-0337. PMC2441685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen Q, Hongu T, Sato T, Zhang Y, Ali W, Cavallo JA, van der Velden A, Tian H, Di Paolo G, Nieswandt B, Kanaho Y, Frohman MA (2012) Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci Signal 5:ra79. https://doi.org/10.1126/scisignal.2003257. PMC3721670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Su W, Yeku O, Olepu S, Genna A, Park JS, Ren H, Du G, Gelb MH, Morris AJ, Frohman MA (2009) 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol Pharmacol 75:437–446. https://doi.org/10.1124/mol.108.053298

    Article  CAS  PubMed  Google Scholar 

  33. Sato T, Hongu T, Sakamoto M, Funakoshi Y, Kanaho Y (2013) Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable. Mol Cell Biol 33:136–145. https://doi.org/10.1128/mcb.00869-12. PMC3536298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Singh NK, Hansen DE 3rd, Kundumani-Sridharan V, Rao GN (2013) Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCgamma-cPLA(2) activation and retinal neovascularization. Blood 121:1911–1923. https://doi.org/10.1182/blood-2012-03-419234. PMC3591809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B (2010) Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal 3:ra1. https://doi.org/10.1126/scisignal.2000551. 3701458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Klier M, Gowert NS, Jackel S, Reinhardt C, Elvers M (2017) Phospholipase D1 is a regulator of platelet-mediated inflammation. Cell Signal 38:171–181. https://doi.org/10.1016/j.cellsig.2017.07.007

    Article  CAS  PubMed  Google Scholar 

  37. Lu WJ, Chung CL, Chen RJ, Huang LT, Lien LM, Chang CC, Lin KH, Sheu JR (2018) An antithrombotic strategy by targeting phospholipase D in human platelets. J Clin Med 7:440. https://doi.org/10.3390/jcm7110440. PMC6262437

    Article  CAS  PubMed Central  Google Scholar 

  38. Holland P, Knaevelsrud H, Soreng K, Mathai BJ, Lystad AH, Pankiv S, Bjorndal GT, Schultz SW, Lobert VH, Chan RB, Zhou B, Liestol K, Carlsson SR, Melia TJ, Di Paolo G, Simonsen A (2016) HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat Commun 7:13889. https://doi.org/10.1038/ncomms13889. PMC5412012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hur JH, Park SY, Dall’Armi C, Lee JS, Di Paolo G, Lee HY, Yoon MS, Min DS, Choi CS (2016) Phospholipase D1 deficiency in mice causes nonalcoholic fatty liver disease via an autophagy defect. Sci Rep 6:39170. https://doi.org/10.1038/srep39170. PMC5156943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dall’Armi C, Hurtado-Lorenzo A, Tian H, Morel E, Nezu A, Chan RB, Yu WH, Robinson KS, Yeku O, Small SA, Duff K, Frohman MA, Wenk MR, Yamamoto A, Di Paolo G (2010) The phospholipase D1 pathway modulates macroautophagy. Nat Commun 1:142. https://doi.org/10.1038/ncomms1144. PMC3328354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cai M, He J, Xiong J, Tay LW, Wang Z, Rog C, Wang J, Xie Y, Wang G, Banno Y, Li F, Zhu M, Du G (2016) Phospholipase D1-regulated autophagy supplies free fatty acids to counter nutrient stress in cancer cells. Cell Death Dis 7:e2448. https://doi.org/10.1038/cddis.2016.355. PMC5260880

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sung TC, Roper RL, Zhang Y, Rudge SA, Temel R, Hammond SM, Morris AJ, Moss B, Engebrecht J, Frohman MA (1997) Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity. Embo J 16:4519–4530. https://doi.org/10.1093/emboj/16.15.4519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vitale N, Caumont AS, Chasserot-Golaz S, Du G, Wu S, Sciorra VA, Morris AJ, Frohman MA, Bader MF (2001) Phospholipase D1: a key factor for the exocytotic machinery in neuroendocrine cells. Embo J 20:2424–2434. https://doi.org/10.1093/emboj/20.10.2424. PMC125248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Disse J, Vitale N, Bader MF, Gerke V (2009) Phospholipase D1 is specifically required for regulated secretion of von Willebrand factor from endothelial cells. Blood 113:973–980. https://doi.org/10.1182/blood-2008-06-165282

    Article  CAS  PubMed  Google Scholar 

  45. Huang J, Haberichter SL, Sadler JE (2012) The B subunits of Shiga-like toxins induce regulated VWF secretion in a phospholipase D1-dependent manner. Blood 120:1143–1149. https://doi.org/10.1182/blood-2012-01-408096. PMC3412335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bolomini-Vittori M, Mennens SFB, Joosten B, Fransen J, Du G, van den Dries K, Cambi A (2019) PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation. Sci Rep 9:3556. https://doi.org/10.1038/s41598-019-39358-0. PMC6401089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Choi WS, Kim YM, Combs C, Frohman MA, Beaven MA (2002) Phospholipases D1 and D2 regulate different phases of exocytosis in mast cells. J Immunol (Baltimore, Md.: 1950) 168:5682–5689. https://doi.org/10.4049/jimmunol.168.11.5682

    Article  CAS  Google Scholar 

  48. Hughes WE, Elgundi Z, Huang P, Frohman MA, Biden TJ (2004) Phospholipase D1 regulates secretagogue-stimulated insulin release in pancreatic beta-cells. J Biol Chem 279:27534–27541. https://doi.org/10.1074/jbc.M403012200

    Article  CAS  PubMed  Google Scholar 

  49. Wang L, Cummings R, Usatyuk P, Morris A, Irani K, Natarajan V (2002) Involvement of phospholipases D1 and D2 in sphingosine 1-phosphate-induced ERK (extracellular-signal-regulated kinase) activation and interleukin-8 secretion in human bronchial epithelial cells. Biochem J 367:751–760. https://doi.org/10.1042/bj20020586. PMC1222936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang Y, Kanaho Y, Frohman MA, Tsirka SE (2005) Phospholipase D1-promoted release of tissue plasminogen activator facilitates neurite outgrowth. J Neurosci 25:1797–1805. https://doi.org/10.1523/jneurosci.4850-04.2005. PMC6725938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Choi HJ, Park SY, Cho JH, Park JW, Sohn JH, Kim YJ, Oh JW, Han JS (2015) The TLR4-associated phospholipase D1 activation is crucial for Der f 2-induced IL-13 production. Allergy 70:1569–1579. https://doi.org/10.1111/all.12764

    Article  CAS  PubMed  Google Scholar 

  52. Mortaz E, Tabarsi P, Mansouri D, Khosravi A, Garssen J, Velayati A, Adcock IM (2016) Cancers related to immunodeficiencies: update and perspectives. Front Immunol 7:365. https://doi.org/10.3389/fimmu.2016.00365. PMC5028721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Buoncervello M, Gabriele L, Toschi E (2019) The Janus Face of tumor microenvironment targeted by immunotherapy. Int J Mol Sci 20:4320. https://doi.org/10.3390/ijms20174320. PMC6747403

    Article  CAS  PubMed Central  Google Scholar 

  54. Ali WH, Chen Q, Delgiorno KE, Su W, Hall JC, Hongu T, Tian H, Kanaho Y, Di Paolo G, Crawford HC, Frohman MA (2013) Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment. PLoS One 8:e55325. https://doi.org/10.1371/journal.pone.0055325. PMC3557251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhu M, Foreman DP, O’Brien SA, Jin Y, Zhang W (2018) Phospholipase D in TCR-mediated signaling and T cell activation. J Immunol (Baltimore, Md.: 1950) 200:2165–2173. https://doi.org/10.4049/jimmunol.1701291. PMC5909698

    Article  CAS  Google Scholar 

  56. Gobel K, Schuhmann MK, Pankratz S, Stegner D, Herrmann AM, Braun A, Breuer J, Bittner S, Ruck T, Wiendl H, Kleinschnitz C, Nieswandt B, Meuth SG (2014) Phospholipase D1 mediates lymphocyte adhesion and migration in experimental autoimmune encephalomyelitis. Eur J Immunol 44:2295–2305. https://doi.org/10.1002/eji.201344107

    Article  CAS  PubMed  Google Scholar 

  57. Mor A, Wynne JP, Ahearn IM, Dustin ML, Du G, Philips MR (2009) Phospholipase D1 regulates lymphocyte adhesion via upregulation of Rap1 at the plasma membrane. Mol Cell Biol 29:3297–3306. https://doi.org/10.1128/mcb.00366-09. PMC2698734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ghim J et al (2014) Endothelial deletion of phospholipase D2 reduces hypoxic response and pathological angiogenesis. Arterioscler Thromb Vasc Biol 34:1697–1703. https://doi.org/10.1161/atvbaha.114.303416

    Article  CAS  PubMed  Google Scholar 

  59. Ngo Thai Bich V, Hongu T, Miura Y, Katagiri N, Ohbayashi N, Yamashita-Kanemaru Y, Shibuya A, Funakoshi Y, Kanaho Y (2018) Physiological function of phospholipase D2 in anti-tumor immunity: regulation of CD8(+) T lymphocyte proliferation. Sci Rep 8:6283. https://doi.org/10.1038/s41598-018-24512-x. PMC5908902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Clancy JW, Zhang Y, Sheehan C, D’Souza-Schorey C (2019) An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nat Cell Biol 21:856–866. https://doi.org/10.1038/s41556-019-0345-y. PMC6697424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G, D’Souza-Schorey C (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19:1875–1885. https://doi.org/10.1016/j.cub.2009.09.059. PMC3150487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Vitale N, Chasserot-Golaz S, Bailly Y, Morinaga N, Frohman MA, Bader MF (2002) Calcium-regulated exocytosis of dense-core vesicles requires the activation of ADP-ribosylation factor (ARF)6 by ARF nucleotide binding site opener at the plasma membrane. J Cell Biol 159:79–89. https://doi.org/10.1083/jcb.200203027. PMC2173505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Munoz-Galvan S, Lucena-Cacace A, Perez M, Otero-Albiol D, Gomez-Cambronero J, Carnero A (2019) Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment. Oncogene 38:1309–1323. https://doi.org/10.1038/s41388-018-0527-2

    Article  CAS  PubMed  Google Scholar 

  64. Egea-Jimenez AL, Zimmermann P (2018) Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles. J Lipid Res 59:1554–1560. https://doi.org/10.1194/jlr.R083964. PMC6121939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ghossoub R, Lembo F, Rubio A, Gaillard CB, Bouchet J, Vitale N, Slavik J, Machala M, Zimmermann P (2014) Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat Commun 5:3477. https://doi.org/10.1038/ncomms4477

    Article  CAS  PubMed  Google Scholar 

  66. Stegner D, Thielmann I, Kraft P, Frohman MA, Stoll G, Nieswandt B (2013) Pharmacological inhibition of phospholipase D protects mice from occlusive thrombus formation and ischemic stroke-brief report. Arterioscl Throm Vasc Biol 33:2212–2217. https://doi.org/10.1161/Atvbaha.113.302030

    Article  CAS  Google Scholar 

  67. Sanematsu F, Nishikimi A, Watanabe M, Hongu T, Tanaka Y, Kanaho Y, Cote JF, Fukui Y (2013) Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation. J Biol Chem 288:8092–8100. https://doi.org/10.1074/jbc.M112.410423. PMC3605628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Monovich L, Mugrage B, Quadros E, Toscano K, Tommasi R, LaVoie S, Liu E, Du Z, LaSala D, Boyar W, Steed P (2007) Optimization of halopemide for phospholipase D2 inhibition. Bioorg Med Chem Lett 17:2310–2311. https://doi.org/10.1016/j.bmcl.2007.01.059

    Article  CAS  PubMed  Google Scholar 

  69. Nelson RK, Ya-Ping J, Gadbery J, Abedeen D, Sampson N, Lin RZ, Frohman MA (2017) Phospholipase D2 loss results in increased blood pressure via inhibition of the endothelial nitric oxide synthase pathway. Sci Rep 7:9112. https://doi.org/10.1038/s41598-017-09852-4. PMC5567230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, Armstrong MD, Arteaga CL, Lindsley CW, Brown HA (2009) Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol 5:108–117. https://doi.org/10.1038/nchembio.140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lee SK, Kim YS, Bae GH, Lee HY, Bae YS (2019) VU0155069 inhibits inflammasome activation independent of phospholipase D1 activity. Sci Rep 9:14349. https://doi.org/10.1038/s41598-019-50806-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Waterson AG, Scott SA, Kett NR, Blobaum AL, Alex Brown H, Lindsley CW (2018) Isoform selective PLD inhibition by novel, chiral 2,8-diazaspiro[4.5]decan-1-one derivatives. Bioorg Med Chem Lett 28:3670–3673. https://doi.org/10.1016/j.bmcl.2018.10.033

    Article  CAS  PubMed  Google Scholar 

  73. Thielmann I, Stegner D, Kraft P, Hagedorn I, Krohne G, Kleinschnitz C, Stoll G, Nieswandt B (2012) Redundant functions of phospholipases D1 and D2 in platelet alpha-granule release. J Thromb Haemost 10:2361–2372. https://doi.org/10.1111/j.1538-7836.2012.04924.x

    Article  CAS  PubMed  Google Scholar 

  74. Kang DW, Lee SW, Hwang WC, Lee BH, Choi YS, Suh YA, Choi KY, Min DS (2017) Phospholipase D1 acts through Akt/TopBP1 and RB1 to regulate the E2F1-dependent apoptotic program in cancer cells. Cancer Res 77:142–152. https://doi.org/10.1158/0008-5472.Can-15-3032

    Article  CAS  PubMed  Google Scholar 

  75. Trujillo Viera J, El-Merahbi R, Nieswandt B, Stegner D, Sumara G (2016) Phospholipases D1 and D2 suppress appetite and protect against overweight. PLoS One 11:e0157607. https://doi.org/10.1371/journal.pone.0157607. PMC4907468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ammar MR, Humeau Y, Hanauer A, Nieswandt B, Bader MF, Vitale N (2013) The Coffin-Lowry syndrome-associated protein RSK2 regulates neurite outgrowth through phosphorylation of phospholipase D1 (PLD1) and synthesis of phosphatidic acid. J Neurosci 33:19470–19479. https://doi.org/10.1523/jneurosci.2283-13.2013. PMC6618760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schonberger T, Jurgens T, Muller J, Armbruster N, Niermann C, Gorressen S, Sommer J, Tian H, di Paolo G, Scheller J, Fischer JW, Gawaz M, Elvers M (2014) Pivotal role of phospholipase D1 in tumor necrosis factor-alpha-mediated inflammation and scar formation after myocardial ischemia and reperfusion in mice. Am J Pathol 184:2450–2464. https://doi.org/10.1016/j.ajpath.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  78. Ta-Shma A, Zhang K, Salimova E, Zernecke A, Sieiro-Mosti D, Stegner D, Furtado M, Shaag A, Perles Z, Nieswandt B, Rein AJ, Rosenthal N, Neiman AM, Elpeleg O (2017) Congenital valvular defects associated with deleterious mutations in the PLD1 gene. J Med Genet 54:278–286. https://doi.org/10.1136/jmedgenet-2016-104259

    Article  CAS  PubMed  Google Scholar 

  79. Wang Z, Zhang F, He J, Wu P, Tay LWR, Cai M, Nian W, Weng Y, Qin L, Chang JT, McIntire LB, Di Paolo G, Xu J, Peng J, Du G (2017) Binding of PLD2-generated phosphatidic acid to KIF5B promotes MT1-MMP surface trafficking and lung metastasis of mouse breast cancer cells. Develop Cell 43:186–197.e187. https://doi.org/10.1016/j.devcel.2017.09.012. PMC5663201

    Article  CAS  Google Scholar 

  80. Henkels KM, Boivin GP, Dudley ES, Berberich SJ, Gomez-Cambronero J (2013) Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model. Oncogene 32:5551–5562. https://doi.org/10.1038/onc.2013.207. PMC3966651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by a Carol Baldwin Breast Cancer award to MAF.

Author information

Authors and Affiliations

  1. Center for Developmental Genetics and the Department of Pharmacological Sciences, Stony Brook University School of Medicine, Stony Brook, NY, USA

    Daniela Barisano & Michael A. Frohman

Authors
  1. Daniela Barisano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Frohman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A. Frohman .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Barisano, D., Frohman, M.A. (2020). Roles for Phospholipase D1 in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1259. Springer, Cham. https://doi.org/10.1007/978-3-030-43093-1_5

Download citation

Publish with us

Policies and ethics

Search

Navigation