Skip to main content
SpringerLink
Log in

Phospholipase Signaling in Breast Cancer

  • Chapter
  • First Online:
Translational Research in Breast Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1187))

Abstract

Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have an impact on cell differentiation, proliferation, migration, and angiogenesis. Phospholipases (PLC, PLD and PLA) are essential mediators of intra- and intercellular signaling. They hydrolyze phospholipids, which are major components of cell membrane that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid. Enzymatic processing of phospholipids by phospholipases converts these molecules into lipid mediators that regulate multiple cellular processes, which in turn can promote breast cancer progression. Thus, dysregulation of phospholipases contributes to a number of human diseases, including cancer. This review describes how phospholipases regulate multiple cancer-associated cellular processes, and the interplay among different phospholipases in breast cancer. A thorough understanding of the breast cancer–associated signaling networks of phospholipases is necessary to determine whether these enzymes are potential targets for innovative therapeutic strategies.

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 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.

    Article  PubMed  Google Scholar 

  2. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9(6):606–16.

    Article  PubMed  Google Scholar 

  3. Jordan VC. Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer. 2007;7(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  4. Rabindran SK. Antitumor activity of HER-2 inhibitors. Cancer Lett. 2005;227(1):9–23.

    Article  CAS  PubMed  Google Scholar 

  5. Linn SC, Van ’t Veer LJ. Clinical relevance of the triple-negative breast cancer concept: genetic basis and clinical utility of the concept. Eur J Cancer. 2009;45(Suppl 1):11–26.

    Article  PubMed  Google Scholar 

  6. van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9(2):112–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Boesze-Battaglia K, Schimmel R. Cell membrane lipid composition and distribution: implications for cell function and lessons learned from photoreceptors and platelets. J Exp Biol. 1997;200(Pt 23):2927–36.

    Article  CAS  PubMed  Google Scholar 

  8. Eyster KM. The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist. Adv Physiol Educ. 2007;31(1):5–16.

    Article  PubMed  Google Scholar 

  9. Spiegel S, Foster D, Kolesnick R. Signal transduction through lipid second messengers. Curr Opin Cell Biol. 1996;8(2):159–67.

    Article  CAS  PubMed  Google Scholar 

  10. Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol. 2008;9(2):162–76.

    Article  CAS  PubMed  Google Scholar 

  11. De Maria L, Vind J, Oxenboll KM, Svendsen A, Patkar S. Phospholipases and their industrial applications. Appl Microbiol Biotechnol. 2007;74(2):290–300.

    Article  CAS  PubMed  Google Scholar 

  12. Ramrakhiani L, Chand S. Recent progress on phospholipases: different sources, assay methods, industrial potential and pathogenicity. Appl Biochem Biotechnol. 2011;164(7):991–1022.

    Article  CAS  PubMed  Google Scholar 

  13. Alzayady KJ, Wang L, Chandrasekhar R, Wagner LE 2nd, Van Petegem F, Yule DI. Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca2+ release. Sci Signal. 2016;9(422):ra35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Suh PG, Park JI, Manzoli L, Cocco L, Peak JC, Katan M, et al. Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep. 2008;41(6):415–34.

    Article  CAS  PubMed  Google Scholar 

  15. Rhee SG. Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem. 2001;70:281–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yang YR, Follo MY, Cocco L, Suh PG. The physiological roles of primary phospholipase C. Adv Biol Regul. 2013;53(3):232–41.

    Article  CAS  PubMed  Google Scholar 

  17. Essen LO, Perisic O, Cheung R, Katan M, Williams RL. Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta. Nature. 1996;380(6575):595–602.

    Article  CAS  PubMed  Google Scholar 

  18. Paterson HF, Savopoulos JW, Perisic O, Cheung R, Ellis MV, Williams RL, et al. Phospholipase C delta 1 requires a pleckstrin homology domain for interaction with the plasma membrane. Biochem J. 1995;312(Pt 3):661–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang T, Dowal L, El-Maghrabi MR, Rebecchi M, Scarlata S. The pleckstrin homology domain of phospholipase C-beta(2) links the binding of gbetagamma to activation of the catalytic core. J Biol Chem. 2000;275(11):7466–9.

    Article  CAS  PubMed  Google Scholar 

  20. Falasca M, Logan SK, Lehto VP, Baccante G, Lemmon MA, Schlessinger J. Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting. EMBO J. 1998;17(2):414–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wen W, Yan J, Zhang M. Structural characterization of the split pleckstrin homology domain in phospholipase C-gamma1 and its interaction with TRPC3. J Biol Chem. 2006;281(17):12060–8.

    Article  CAS  PubMed  Google Scholar 

  22. Nakashima S, Banno Y, Watanabe T, Nakamura Y, Mizutani T, Sakai H, et al. Deletion and site-directed mutagenesis of EF-hand domain of phospholipase C-delta 1: effects on its activity. Biochem Biophys Res Commun. 1995;211(2):365–9.

    Article  CAS  PubMed  Google Scholar 

  23. Otterhag L, Sommarin M, Pical C. N-terminal EF-hand-like domain is required for phosphoinositide-specific phospholipase C activity in Arabidopsis thaliana. FEBS Lett. 2001;497(2–3):165–70.

    Article  CAS  PubMed  Google Scholar 

  24. Rhee SG. Reflections on the days of phospholipase C. Adv Biol Regul. 2013;53(3):223–31.

    Article  CAS  PubMed  Google Scholar 

  25. Rebecchi MJ, Pentyala SN. Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev. 2000;80(4):1291–335.

    Article  CAS  PubMed  Google Scholar 

  26. Drin G, Scarlata S. Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding--how many ways can you activate an enzyme? Cell Signal. 2007;19(7):1383–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kamat A, Carpenter G. Phospholipase C-gamma1: regulation of enzyme function and role in growth factor-dependent signal transduction. Cytokine Growth Factor Rev. 1997;8(2):109–17.

    Article  CAS  PubMed  Google Scholar 

  28. Smrcka AV, Brown JH, Holz GG. Role of phospholipase Cepsilon in physiological phosphoinositide signaling networks. Cell Signal. 2012;24(6):1333–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jin TG, Satoh T, Liao Y, Song C, Gao X, Kariya K, et al. Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling. J Biol Chem. 2001;276(32):30301–7.

    Article  CAS  PubMed  Google Scholar 

  30. Thore S, Dyachok O, Tengholm A. Oscillations of phospholipase C activity triggered by depolarization and Ca2+ influx in insulin-secreting cells. J Biol Chem. 2004;279(19):19396–400.

    Article  CAS  PubMed  Google Scholar 

  31. Young KW, Nash MS, Challiss RA, Nahorski SR. Role of Ca2+ feedback on single cell inositol 1,4,5-trisphosphate oscillations mediated by G-protein-coupled receptors. J Biol Chem. 2003;278(23):20753–60.

    Article  CAS  PubMed  Google Scholar 

  32. Kim JK, Choi JW, Lim S, Kwon O, Seo JK, Ryu SH, et al. Phospholipase C-eta1 is activated by intracellular Ca(2+) mobilization and enhances GPCRs/PLC/Ca(2+) signaling. Cell Signal. 2011;23(6):1022–9.

    Article  CAS  PubMed  Google Scholar 

  33. Peng X, Frohman MA. Mammalian phospholipase D physiological and pathological roles. Acta Physiol (Oxf). 2012;204(2):219–26.

    Article  CAS  Google Scholar 

  34. Saito M, Kanfer J. Phosphatidohydrolase activity in a solubilized preparation from rat brain particulate fraction. Arch Biochem Biophys. 1975;169(1):318–23.

    Article  CAS  PubMed  Google Scholar 

  35. Osisami M, Ali W, Frohman MA. A role for phospholipase D3 in myotube formation. PLoS One. 2012;7(3):e33341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yoshikawa F, Banno Y, Otani Y, Yamaguchi Y, Nagakura-Takagi Y, Morita N, et al. Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expression in spleen and early postnatal microglia. PLoS One. 2010;5(11):e13932.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Choi SY, Huang P, Jenkins GM, Chan DC, Schiller J, Frohman MA. A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nat Cell Biol. 2006;8(11):1255–62.

    Article  CAS  PubMed  Google Scholar 

  38. Ha EE, Frohman MA. Regulation of mitochondrial morphology by lipids. Biofactors. 2014;40(4):419–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Song J, Jiang YW, Foster DA. Epidermal growth factor induces the production of biologically distinguishable diglyceride species from phosphatidylinositol and phosphatidylcholine via the independent activation of type C and type D phospholipases. Cell Growth Differ. 1994;5(1):79–85.

    CAS  PubMed  Google Scholar 

  40. Plevin R, Cook SJ, Palmer S, Wakelam MJ. Multiple sources of sn-1,2-diacylglycerol in platelet-derived-growth-factor-stimulated Swiss 3T3 fibroblasts. Evidence for activation of phosphoinositidase C and phosphatidylcholine-specific phospholipase D. Biochem J. 1991;279(Pt 2):559–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Motoike T, Bieger S, Wiegandt H, Unsicker K. Induction of phosphatidic acid by fibroblast growth factor in cultured baby hamster kidney fibroblasts. FEBS Lett. 1993;332(1–2):164–8.

    Article  CAS  PubMed  Google Scholar 

  42. Frohman MA, Sung TC, Morris AJ. Mammalian phospholipase D structure and regulation. Biochim Biophys Acta. 1999;1439(2):175–86.

    Article  CAS  PubMed  Google Scholar 

  43. Exton JH. Regulation of phospholipase D. FEBS Lett. 2002;531(1):58–61.

    Article  CAS  PubMed  Google Scholar 

  44. Brown FD, Thompson N, Saqib KM, Clark JM, Powner D, Thompson NT, et al. Phospholipase D1 localises to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulation. Curr Biol. 1998;8(14):835–8.

    Article  CAS  PubMed  Google Scholar 

  45. Freyberg Z, Sweeney D, Siddhanta A, Bourgoin S, Frohman M, Shields D. Intracellular localization of phospholipase D1 in mammalian cells. Mol Biol Cell. 2001;12(4):943–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Du G, Huang P, Liang BT, Frohman MA. Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis. Mol Biol Cell. 2004;15(3):1024–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, et al. Phospholipase signalling networks in cancer. Nat Rev Cancer. 2012;12(11):782–92.

    Article  CAS  PubMed  Google Scholar 

  48. Ammar MR, Kassas N, Chasserot-Golaz S, Bader MF, Vitale N. Lipids in regulated exocytosis: what are they doing? Front Endocrinol (Lausanne). 2013;4:125.

    Article  Google Scholar 

  49. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009;324(5925):384–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhao C, Du G, Skowronek K, Frohman MA, Bar-Sagi D. Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol. 2007;9(6):706–12.

    Article  CAS  PubMed  Google Scholar 

  51. Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, et al. Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell. 1999;99(5):521–32.

    Article  CAS  PubMed  Google Scholar 

  52. Jang JH, Lee CS, Hwang D, Ryu SH. Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog Lipid Res. 2012;51(2):71–81.

    Article  CAS  PubMed  Google Scholar 

  53. Aoki J. Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol. 2004;15(5):477–89.

    Article  CAS  PubMed  Google Scholar 

  54. Csaki LS, Dwyer JR, Fong LG, Tontonoz P, Young SG, Reue K. Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling. Prog Lipid Res. 2013;52(3):305–16.

    Article  CAS  PubMed  Google Scholar 

  55. Aoki J, Inoue A, Makide K, Saiki N, Arai H. Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family. Biochimie. 2007;89(2):197–204.

    Article  CAS  PubMed  Google Scholar 

  56. Murakami M, Taketomi Y, Miki Y, Sato H, Hirabayashi T, Yamamoto K. Recent progress in phospholipase A(2) research: from cells to animals to humans. Prog Lipid Res. 2011;50(2):152–92.

    Article  CAS  PubMed  Google Scholar 

  57. Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 2002;68–69:3–58.

    Article  PubMed  Google Scholar 

  58. Hirabayashi T, Murayama T, Shimizu T. Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biol Pharm Bull. 2004;27(8):1168–73.

    Article  CAS  PubMed  Google Scholar 

  59. Nakanishi M, Rosenberg DW. Roles of cPLA2alpha and arachidonic acid in cancer. Biochim Biophys Acta. 2006;1761(11):1335–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Oude Weernink PA, Lopez de Jesus M, Schmidt M. Phospholipase D signaling: orchestration by PIP2 and small GTPases. Naunyn Schmiedeberg’s Arch Pharmacol. 2007;374(5–6):399–411.

    Article  CAS  Google Scholar 

  61. Cho CH, Lee CS, Chang M, Jang IH, Kim SJ, Hwang I, et al. Localization of VEGFR-2 and PLD2 in endothelial caveolae is involved in VEGF-induced phosphorylation of MEK and ERK. Am J Physiol Heart Circ Physiol. 2004;286(5):H1881–8.

    Article  CAS  PubMed  Google Scholar 

  62. Alberghina M. Phospholipase A(2): new lessons from endothelial cells. Microvasc Res. 2010;80(2):280–5.

    Article  CAS  PubMed  Google Scholar 

  63. Lee CS, Kim KL, Jang JH, Choi YS, Suh PG, Ryu SH. The roles of phospholipase D in EGFR signaling. Biochim Biophys Acta. 2009;1791(9):862–8.

    Article  CAS  PubMed  Google Scholar 

  64. Wang X, Devaiah SP, Zhang W, Welti R. Signaling functions of phosphatidic acid. Prog Lipid Res. 2006;45(3):250–78.

    Article  CAS  PubMed  Google Scholar 

  65. Wen R, Chen Y, Bai L, Fu G, Schuman J, Dai X, et al. Essential role of phospholipase C gamma 2 in early B-cell development and Myc-mediated lymphomagenesis. Mol Cell Biol. 2006;26(24):9364–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wakita M, Edamatsu H, Li M, Emi A, Kitazawa S, Kataoka T. Phospholipase C activates nuclear factor-kappaB signaling by causing cytoplasmic localization of ribosomal S6 kinase and facilitating its phosphorylation of inhibitor kappaB in Colon epithelial cells. J Biol Chem. 2016;291(24):12586–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yoshida N, Amanai M, Fukui T, Kajikawa E, Brahmajosyula M, Iwahori A, et al. Broad, ectopic expression of the sperm protein PLCZ1 induces parthenogenesis and ovarian tumours in mice. Development. 2007;134(21):3941–52.

    Article  CAS  PubMed  Google Scholar 

  68. Bertagnolo V, Benedusi M, Querzoli P, Pedriali M, Magri E, Brugnoli F, et al. PLC-beta2 is highly expressed in breast cancer and is associated with a poor outcome: a study on tissue microarrays. Int J Oncol. 2006;28(4):863–72.

    CAS  PubMed  Google Scholar 

  69. Bertagnolo V, Benedusi M, Brugnoli F, Lanuti P, Marchisio M, Querzoli P, et al. Phospholipase C-beta 2 promotes mitosis and migration of human breast cancer-derived cells. Carcinogenesis. 2007;28(8):1638–45.

    Article  CAS  PubMed  Google Scholar 

  70. Sengelaub CA, Navrazhina K, Ross JB, Halberg N, Tavazoie SF. PTPRN2 and PLCbeta1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling. EMBO J. 2016;35(1):62–76.

    Article  CAS  PubMed  Google Scholar 

  71. Cai S, Sun PH, Resaul J, Shi L, Jiang A, Satherley LK, et al. Expression of phospholipase C isozymes in human breast cancer and their clinical significance. Oncol Rep. 2017;37(3):1707–15.

    Article  CAS  PubMed  Google Scholar 

  72. Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL. Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. Proc Natl Acad Sci U S A. 1991;88(23):10435–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Noh DY, Lee YH, Kim SS, Kim YI, Ryu SH, Suh PG, et al. Elevated content of phospholipase C-gamma 1 in colorectal cancer tissues. Cancer. 1994;73(1):36–41.

    Article  CAS  PubMed  Google Scholar 

  74. Shepard CR, Kassis J, Whaley DL, Kim HG, Wells A. PLC gamma contributes to metastasis of in situ-occurring mammary and prostate tumors. Oncogene. 2007;26(21):3020–6.

    Article  CAS  PubMed  Google Scholar 

  75. Noh DY, Kang HS, Kim YC, Youn YK, Oh SK, Choe KJ, et al. Expression of phospholipase C-gamma 1 and its transcriptional regulators in breast cancer tissues. Anticancer Res. 1998;18(4a):2643–8.

    CAS  PubMed  Google Scholar 

  76. Balz LM, Bartkowiak K, Andreas A, Pantel K, Niggemann B, Zanker KS, et al. The interplay of HER2/HER3/PI3K and EGFR/HER2/PLC-gamma1 signalling in breast cancer cell migration and dissemination. J Pathol. 2012;227(2):234–44.

    Article  CAS  PubMed  Google Scholar 

  77. Shien T, Doihara H, Hara H, Takahashi H, Yoshitomi S, Taira N, et al. PLC and PI3K pathways are important in the inhibition of EGF-induced cell migration by gefitinib (‘Iressa’, ZD1839). Breast Cancer. 2004;11(4):367–73.

    Article  PubMed  Google Scholar 

  78. Piccolo E, Innominato PF, Mariggio MA, Maffucci T, Iacobelli S, Falasca M. The mechanism involved in the regulation of phospholipase Cgamma1 activity in cell migration. Oncogene. 2002;21(42):6520–9.

    Article  CAS  PubMed  Google Scholar 

  79. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, et al. Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res. 2008;68(24):10187–96.

    Article  CAS  PubMed  Google Scholar 

  80. Uhlmann S, Zhang JD, Schwager A, Mannsperger H, Riazalhosseini Y, Burmester S, et al. miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer. Oncogene. 2010;29(30):4297–306.

    Article  CAS  PubMed  Google Scholar 

  81. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.

    Article  CAS  PubMed  Google Scholar 

  82. Lim YY, Wright JA, Attema JL, Gregory PA, Bert AG, Smith E, et al. Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state. J Cell Sci. 2013;126(Pt 10):2256–66.

    Article  CAS  PubMed  Google Scholar 

  83. Leung DW, Tompkins C, Brewer J, Ball A, Coon M, Morris V, et al. Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells. Mol Cancer. 2004;3:15.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Nakamura Y, Fukami K, Yu H, Takenaka K, Kataoka Y, Shirakata Y, et al. Phospholipase Cdelta1 is required for skin stem cell lineage commitment. EMBO J. 2003;22(12):2981–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bai Y, Edamatsu H, Maeda S, Saito H, Suzuki N, Satoh T, et al. Crucial role of phospholipase Cepsilon in chemical carcinogen-induced skin tumor development. Cancer Res. 2004;64(24):8808–10.

    Article  CAS  PubMed  Google Scholar 

  86. Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H, et al. Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell. 2009;16(2):161–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Fu L, Qin YR, Xie D, Hu L, Kwong DL, Srivastava G, et al. Characterization of a novel tumor-suppressor gene PLC delta 1 at 3p22 in esophageal squamous cell carcinoma. Cancer Res. 2007;67(22):10720–6.

    Article  CAS  PubMed  Google Scholar 

  88. Rebecchi MJ, Raghubir A, Scarlata S, Hartenstine MJ, Brown T, Stallings JD. Expression and function of phospholipase C in breast carcinoma. Adv Enzym Regul. 2009;49(1):59–73.

    Article  CAS  Google Scholar 

  89. Mu H, Wang N, Zhao L, Li S, Li Q, Chen L, et al. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer. Exp Cell Res. 2015;332(2):179–89.

    Article  CAS  PubMed  Google Scholar 

  90. Uchida N, Okamura S, Nagamachi Y, Yamashita S. Increased phospholipase D activity in human breast cancer. J Cancer Res Clin Oncol. 1997;123(5):280–5.

    Article  CAS  PubMed  Google Scholar 

  91. Noh DY, Ahn SJ, Lee RA, Park IA, Kim JH, Suh PG, et al. Overexpression of phospholipase D1 in human breast cancer tissues. Cancer Lett. 2000;161(2):207–14.

    Article  CAS  PubMed  Google Scholar 

  92. Gozgit JM, Pentecost BT, Marconi SA, Ricketts-Loriaux RSJ, Otis CN, Arcaro KF. PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas. Br J Cancer. 2007;97(6):809–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Ye Q, Kantonen S, Henkels KM, Gomez-Cambronero J. A new signaling pathway (JAK-Fes-phospholipase D) that is enhanced in highly proliferative breast cancer cells. J Biol Chem. 2013;288(14):9881–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chen Q, Hongu T, Sato T, Zhang Y, Ali W, Cavallo JA, et al. Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci Signal. 2012;5(249):ra79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318(5853):1108–13.

    Article  CAS  PubMed  Google Scholar 

  96. Hong KW, Jin HS, Lim JE, Cho YS, Go MJ, Jung J, et al. Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension. J Hum Hypertens. 2010;24(11):763–74.

    Article  CAS  PubMed  Google Scholar 

  97. Carnero A, Cuadrado A, del Peso L, Lacal JC. Activation of type D phospholipase by serum stimulation and ras-induced transformation in NIH3T3 cells. Oncogene. 1994;9(5):1387–95.

    CAS  PubMed  Google Scholar 

  98. Frankel P, Ramos M, Flom J, Bychenok S, Joseph T, Kerkhoff E, et al. Ral and Rho-dependent activation of phospholipase D in v-Raf-transformed cells. Biochem Biophys Res Commun. 1999;255(2):502–7.

    Article  CAS  PubMed  Google Scholar 

  99. Song JG, Pfeffer LM, Foster DA. v-Src increases diacylglycerol levels via a type D phospholipase-mediated hydrolysis of phosphatidylcholine. Mol Cell Biol. 1991;11(10):4903–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rizzo MA, Shome K, Vasudevan C, Stolz DB, Sung TC, Frohman MA, et al. Phospholipase D and its product, phosphatidic acid, mediate agonist-dependent raf-1 translocation to the plasma membrane and the activation of the mitogen-activated protein kinase pathway. J Biol Chem. 1999;274(2):1131–9.

    Article  CAS  PubMed  Google Scholar 

  101. Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science. 2001;294(5548):1942–5.

    Article  CAS  PubMed  Google Scholar 

  102. Toschi A, Lee E, Xu L, Garcia A, Gadir N, Foster DA. Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Mol Cell Biol. 2009;29(6):1411–20.

    Article  CAS  PubMed  Google Scholar 

  103. Hui L, Zheng Y, Yan Y, Bargonetti J, Foster DA. Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D. Oncogene. 2006;25(55):7305–10.

    Article  CAS  PubMed  Google Scholar 

  104. Zheng Y, Rodrik V, Toschi A, Shi M, Hui L, Shen Y, et al. Phospholipase D couples survival and migration signals in stress response of human cancer cells. J Biol Chem. 2006;281(23):15862–8.

    Article  CAS  PubMed  Google Scholar 

  105. Thapa N, Anderson RA. PLD and PA take MT1-MMP for a metastatic ride. Dev Cell. 2017;43(2):117–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wang Z, Zhang F, He J, Wu P, Tay LWR, Cai M, et al. Binding of PLD2-generated Phosphatidic acid to KIF5B promotes MT1-MMP surface trafficking and lung metastasis of mouse breast Cancer cells. Dev Cell. 2017;43(2):186–97.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Du G, Wang Z, Zhang F, Rog C, Lu M, Peng J, et al. Phospholipase D2 regulation of MT1-MMP membrane trafficking promotes breast cancer metastasis. FASEB J. 2015;29(1_Suppl):715–24.

    Google Scholar 

  108. Henkels KM, Boivin GP, Dudley ES, Berberich SJ, Gomez-Cambronero J. Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model. Oncogene. 2013;32(49):5551–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kang DW, Choi CY, Cho YH, Tian H, Di Paolo G, Choi KY, et al. Targeting phospholipase D1 attenuates intestinal tumorigenesis by controlling beta-catenin signaling in cancer-initiating cells. J Exp Med. 2015;212(8):1219–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kang DW, Lee SW, Hwang WC, Lee BH, Choi YS, Suh YA, et al. Phospholipase D1 acts through Akt/TopBP1 and RB1 to regulate the E2F1-dependent apoptotic program in Cancer cells. Cancer Res. 2017;77(1):142–52.

    Article  CAS  PubMed  Google Scholar 

  111. Ghim J, Moon JS, Lee CS, Lee J, Song P, Lee A, et al. Endothelial deletion of phospholipase D2 reduces hypoxic response and pathological angiogenesis. Arterioscler Thromb Vasc Biol. 2014;34(8):1697–703.

    Article  CAS  PubMed  Google Scholar 

  112. Yamashita S, Yamashita J, Ogawa M. Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. Br J Cancer. 1994;69(6):1166–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Caiazza F, McCarthy NS, Young L, Hill AD, Harvey BJ, Thomas W. Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours. Br J Cancer. 2011;104(2):338–44.

    Article  CAS  PubMed  Google Scholar 

  114. Caiazza F, Harvey BJ, Thomas W. Cytosolic phospholipase A2 activation correlates with HER2 overexpression and mediates estrogen-dependent breast cancer cell growth. Mol Endocrinol. 2010;24(5):953–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Chen L, Fu H, Luo Y, Chen L, Cheng R, Zhang N, et al. cPLA2alpha mediates TGF-beta-induced epithelial-mesenchymal transition in breast cancer through PI3k/Akt signaling. Cell Death Dis. 2017;8(4):e2728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Brglez V, Pucer A, Pungercar J, Lambeau G, Petan T. Secreted phospholipases A(2)are differentially expressed and epigenetically silenced in human breast cancer cells. Biochem Biophys Res Commun. 2014;445(1):230–5.

    Article  CAS  PubMed  Google Scholar 

  117. Ilsley JN, Nakanishi M, Flynn C, Belinsky GS, De Guise S, Adib JN, et al. Cytoplasmic phospholipase A2 deletion enhances colon tumorigenesis. Cancer Res. 2005;65(7):2636–43.

    Article  CAS  PubMed  Google Scholar 

  118. Hong KH, Bonventre JC, O'Leary E, Bonventre JV, Lander ES. Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis. Proc Natl Acad Sci U S A. 2001;98(7):3935–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Harizi H, Corcuff JB, Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med. 2008;14(10):461–9.

    Article  CAS  PubMed  Google Scholar 

  120. Buczynski MW, Dumlao DS, Dennis EA. Thematic review series: proteomics. An integrated omics analysis of eicosanoid biology. J Lipid Res. 2009;50(6):1015–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294(5548):1871–5.

    Article  CAS  PubMed  Google Scholar 

  122. Stafforini DM, McIntyre TM, Carter ME, Prescott SM. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor. J Biol Chem. 1987;262(9):4215–22.

    Article  CAS  PubMed  Google Scholar 

  123. Montrose DC, Nakanishi M, Murphy RC, Zarini S, McAleer JP, Vella AT, et al. The role of PGE2 in intestinal inflammation and tumorigenesis. Prostaglandins Other Lipid Mediat. 2015;116–117:26–36.

    Article  PubMed  CAS  Google Scholar 

  124. Mauritz I, Westermayer S, Marian B, Erlach N, Grusch M, Holzmann K. Prostaglandin E(2) stimulates progression-related gene expression in early colorectal adenoma cells. Br J Cancer. 2006;94(11):1718–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Rosch S, Ramer R, Brune K, Hinz B. Prostaglandin E2 induces cyclooxygenase-2 expression in human non-pigmented ciliary epithelial cells through activation of p38 and p42/44 mitogen-activated protein kinases. Biochem Biophys Res Commun. 2005;338(2):1171–8.

    Article  PubMed  CAS  Google Scholar 

  126. Richards JA, Petrel TA, Brueggemeier RW. Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells. J Steroid Biochem Mol Biol. 2002;80(2):203–12.

    Article  CAS  PubMed  Google Scholar 

  127. Meyer AM, Dwyer-Nield LD, Hurteau GJ, Keith RL, O'Leary E, You M, et al. Decreased lung tumorigenesis in mice genetically deficient in cytosolic phospholipase A2. Carcinogenesis. 2004;25(8):1517–24.

    Article  CAS  PubMed  Google Scholar 

  128. Cormier RT, Bilger A, Lillich AJ, Halberg RB, Hong KH, Gould KA, et al. The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogene. 2000;19(28):3182–92.

    Article  CAS  PubMed  Google Scholar 

  129. Papanikolaou A, Wang QS, Mulherkar R, Bolt A, Rosenberg DW. Expression analysis of the group IIA secretory phospholipase A(2) in mice with differential susceptibility to azoxymethane-induced colon tumorigenesis. Carcinogenesis. 2000;21(2):133–8.

    Article  CAS  PubMed  Google Scholar 

  130. Linkous AG, Yazlovitskaya EM, Hallahan DE. Cytosolic phospholipase A2 and lysophospholipids in tumor angiogenesis. J Natl Cancer Inst. 2010;102(18):1398–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buchberg AM. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell. 1995;81(6):957–66.

    Article  CAS  PubMed  Google Scholar 

  132. McHowat J, Gullickson G, Hoover RG, Sharma J, Turk J, Kornbluth J. Platelet-activating factor and metastasis: calcium-independent phospholipase A2beta deficiency protects against breast cancer metastasis to the lung. Am J Physiol Cell Physiol. 2011;300(4):C825–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer. 2003;3(8):582–91.

    Article  CAS  PubMed  Google Scholar 

  134. Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q, et al. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med. 2006;203(4):941–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Li H, Zhao Z, Wei G, Yan L, Wang D, Zhang H, et al. Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development. FASEB J. 2010;24(10):4103–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochem J. 1995;309(Pt 3):933–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Fang X, Gaudette D, Furui T, Mao M, Estrella V, Eder A, et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann N Y Acad Sci. 2000;905:188–208.

    Article  CAS  PubMed  Google Scholar 

  138. Sasagawa T, Okita M, Murakami J, Kato T, Watanabe A. Abnormal serum lysophospholipids in multiple myeloma patients. Lipids. 1999;34(1):17–21.

    Article  CAS  PubMed  Google Scholar 

  139. Goetzl EJ, Dolezalova H, Kong Y, Hu YL, Jaffe RB, Kalli KR, et al. Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res. 1999;59(20):5370–5.

    CAS  PubMed  Google Scholar 

  140. Pustilnik TB, Estrella V, Wiener JR, Mao M, Eder A, Watt MA, et al. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin Cancer Res. 1999;5(11):3704–10.

    CAS  PubMed  Google Scholar 

  141. Schulte KM, Beyer A, Kohrer K, Oberhauser S, Roher HD. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer. 2001;92(2):249–56.

    Article  CAS  PubMed  Google Scholar 

  142. Villegas-Comonfort S, Serna-Marquez N, Galindo-Hernandez O, Navarro-Tito N, Salazar EP. Arachidonic acid induces an increase of beta-1,4-galactosyltransferase I expression in MDA-MB-231 breast cancer cells. J Cell Biochem. 2012;113(11):3330–41.

    Article  CAS  PubMed  Google Scholar 

  143. Boucharaba A, Serre CM, Gres S, Saulnier-Blache JS, Bordet JC, Guglielmi J, et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest. 2004;114(12):1714–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Wang D, DuBois RN. Eicosanoids and cancer. Nat Rev Cancer. 2010;10(3):181–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Poczobutt JM, Gijon M, Amin J, Hanson D, Li H, Walker D, et al. Eicosanoid profiling in an orthotopic model of lung cancer progression by mass spectrometry demonstrates selective production of leukotrienes by inflammatory cells of the microenvironment. PLoS One. 2013;8(11):e79633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Herbert SP, Ponnambalam S, Walker JH. Cytosolic phospholipase A2-alpha mediates endothelial cell proliferation and is inactivated by association with the Golgi apparatus. Mol Biol Cell. 2005;16(8):3800–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Herbert SP, Odell AF, Ponnambalam S, Walker JH. Activation of cytosolic phospholipase A2-{alpha} as a novel mechanism regulating endothelial cell cycle progression and angiogenesis. J Biol Chem. 2009;284(9):5784–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010;16(3):876–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Akiba S, Sato T. Cellular function of calcium-independent phospholipase A2. Biol Pharm Bull. 2004;27(8):1174–8.

    Article  CAS  PubMed  Google Scholar 

  150. Ong WY, Farooqui T, Farooqui AA. Involvement of cytosolic phospholipase A(2), calcium independent phospholipase A(2) and plasmalogen selective phospholipase A(2) in neurodegenerative and neuropsychiatric conditions. Curr Med Chem. 2010;17(25):2746–63.

    Article  CAS  PubMed  Google Scholar 

  151. Burgdorf C, Schafer U, Richardt G, Kurz T. U73122, an aminosteroid phospholipase C inhibitor, is a potent inhibitor of cardiac phospholipase D by a PIP2-dependent mechanism. J Cardiovasc Pharmacol. 2010;55(6):555–9.

    Article  CAS  PubMed  Google Scholar 

  152. Feisst C, Albert D, Steinhilber D, Werz O. The aminosteroid phospholipase C antagonist U-73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5- dione) potently inhibits human 5-lipoxygenase in vivo and in vitro. Mol Pharmacol. 2005;67(5):1751–7.

    Article  CAS  PubMed  Google Scholar 

  153. Hollywood MA, Sergeant GP, Thornbury KD, McHale NG. The PI-PLC inhibitor U-73122 is a potent inhibitor of the SERCA pump in smooth muscle. Br J Pharmacol. 2010;160(6):1293–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38(6):698–707.

    Article  CAS  PubMed  Google Scholar 

  155. Samoha S, Arber N. Cyclooxygenase-2 inhibition prevents colorectal cancer: from the bench to the bed side. Oncology. 2005;69(Suppl 1):33–7.

    Article  CAS  PubMed  Google Scholar 

  156. Chakraborti AK, Garg SK, Kumar R, Motiwala HF, Jadhavar PS. Progress in COX-2 inhibitors: a journey so far. Curr Med Chem. 2010;17(15):1563–93.

    Article  CAS  PubMed  Google Scholar 

  157. Fraser H, Hislop C, Christie RM, Rick HL, Reidy CA, Chouinard ML, et al. Varespladib (A-002), a secretory phospholipase A2 inhibitor, reduces atherosclerosis and aneurysm formation in ApoE−/− mice. J Cardiovasc Pharmacol. 2009;53(1):60–5.

    Article  CAS  PubMed  Google Scholar 

  158. Su W, Yeku O, Olepu S, Genna A, Park JS, Ren H, et al. 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol Pharmacol. 2009;75(3):437–46.

    Article  CAS  PubMed  Google Scholar 

  159. Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, et al. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol. 2009;5(2):108–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Brown HA, Thomas PG, Lindsley CW. Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nat Rev Drug Discov. 2017;16(5):351–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG. Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1. Biochemistry. 2000;39(29):8674–82.

    Article  CAS  PubMed  Google Scholar 

  162. Jones NP, Katan M. Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1. Mol Cell Biol. 2007;27(16):5790–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea

    Yu Jin Lee, Kyeong Jin Shin, Hyun-Jun Jang & Pann-Ghill Suh

  2. Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea

    Dong-Young Noh

  3. Gangnam CHA Medical Center, Seoul, South Korea

    Dong-Young Noh

  4. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea

    Sung Ho Ryu

  5. Korea Brain Research Institute, Daegu, Republic of Korea

    Pann-Ghill Suh

Authors
  1. Yu Jin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyeong Jin Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun-Jun Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong-Young Noh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung Ho Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pann-Ghill Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pann-Ghill Suh .

Editor information

Editors and Affiliations

  1. Department of Surgery, College of Medicine, Seoul National University, Seoul, Korea (Republic of)

    Dong-Young Noh

  2. College of Medicine, Seoul National University College of Medicine, Seoul, Korea (Republic of)

    Wonshik Han

  3. Graduate School of Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Masakazu Toi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lee, Y.J., Shin, K.J., Jang, HJ., Noh, DY., Ryu, S.H., Suh, PG. (2021). Phospholipase Signaling in Breast Cancer. In: Noh, DY., Han, W., Toi, M. (eds) Translational Research in Breast Cancer. Advances in Experimental Medicine and Biology, vol 1187. Springer, Singapore. https://doi.org/10.1007/978-981-32-9620-6_2

Download citation

Publish with us

Policies and ethics

Search

Navigation