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Phospholipase C-γ1 in tumor progression

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Abstract

The vast majority of cancer morbidity and mortality arises from tumor progression beyond the primary tumor site. Unfortunately, most therapies are not effective for advanced stage disease with regional extension or distant metastases. Thus, new treatments are needed to target rate limiting steps in tumor progression. The ability of cancers to invade and metastasize requires the acquisition of specific cell behaviors that enable the cell to escape from the localized site, breach the defined boundaries, reach a hospitable ectopic site and grow in this new locale. Recently, dysregulation of cell motility as stimulated by various extracellular factors has gained credence as a rate-limiting alteration in tumor progression in carcinomas and some other solid tumors. This has focused attention on initiators of signaling cascades that regulate tumor migration. In this effort, one molecule, phospholipase C-γ1 (PLCγ), has been shown to function as a key molecular switch.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Liao H-J, Kume T, McKay C et al. Absence of erythrogenesis and vasculogenesis in Plcg 1-deficient mice. J Biol Chem 2002; 277: 9335–41.

    Article  PubMed  CAS  Google Scholar 

  3. Homma MK, Yamasaki M, Ohmi S et al. Inhibition of phosphoinositide hydrolysis and cell growth of Swiss 3T3 cells by myristoylated phospholipase C inhibitor peptides. J Biochem 1997; 122: 738–42.

    PubMed  CAS  Google Scholar 

  4. Haugh JM, Schooler K, Wells A et al. Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-? signaling pathway. J Biol Chem 1999; 274: 8958–65.

    Article  PubMed  CAS  Google Scholar 

  5. Haugh JM, Meyer T. Active EGF receptors have limited access to Ptdlns(4,5)P-2 in endosomes: Implications for phospholipase C and PI 3-kinase signaling. J Cell Sci 2002; 115: 303–10.

    Google Scholar 

  6. Matsuda M, Paterson HF, Rodriguez P et al. Real time fluorescence imaging of PLC? translocation and its interaction with the epidermal growth factor receptor. J Cell Biol 2001; 153: 599–612.

    Article  PubMed  CAS  Google Scholar 

  7. Ji Q-S, Ermini S, Baulida J et al. Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts. Mol Biol Cell 1998; 9: 749–57.

    PubMed  CAS  Google Scholar 

  8. Chen P, Xie H, Sekar MC et al. Epidermal growth factor receptormediated cell motility: Phospholipase C activity is required, but MAP kinase activity is not sufficient for induced cell movement. J Cell Biol 1994; 127: 847–57.

    Article  PubMed  CAS  Google Scholar 

  9. Turner T, VanEpps-Fung M, Kassis J, et al. Molecular inhibition of PLC? signaling abrogates DU-145 prostate tumor cell invasion. Clin Cancer Res 1997; 3: 2275–82.

    PubMed  CAS  Google Scholar 

  10. Valius M, Kazlauskas A. Phospholipase C-? 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell 1993; 73: 321–34.

    Article  PubMed  CAS  Google Scholar 

  11. Wang Z, Gluck S, Zhang L et al. Requirement for phospholipase C?-1 enzymatic activity in growth factor-induced mitogenesis. Mol Cell Biol 1998; 18: 590–7.

    PubMed  CAS  Google Scholar 

  12. Wells A, Kassis J, Solava J et al. Growth factor-induced cell motility in tumor invasion. Acta Oncol 2002; 41: 124–30.

    Article  PubMed  CAS  Google Scholar 

  13. Wells A. Tumor invasion: Role of growth factor-induced cell motility. Adv Cancer Res 2000; 78: 31–101.

    Article  PubMed  CAS  Google Scholar 

  14. Kundra V, Escobedo JA, Kazlauskas A et al. Regulation of chemotaxis by the platelet-derived growth factor receptor-?. Nature 1994; 367: 474–6.

    Article  PubMed  CAS  Google Scholar 

  15. Bornfeldt KE, Raines EW, Nakano T et al. Insulin-like growth factor-1 and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signalling pathways that are distinct from those of proliferation. J Clin Invest 1994; 93: 1266–74.

    PubMed  CAS  Google Scholar 

  16. Derman MP, Chen JY, Spokes KC et al. An 11-amino acid sequence from c-met initiates epithelial chemotaxis via phosphatidylinositol 3-kinase and phospholipase C. J Biol Chem 1996; 271: 4251–5.

    Article  PubMed  CAS  Google Scholar 

  17. Clyman RI, Peters KG, Chen YQ et al. Phospholipase C-? activation, phosphotidylinositol hydrolysis, and calcium mobilization are not required for FGF receptor-mediated chemotaxis. Cell Adhes Commun 1994; 1: 333–42.

    PubMed  CAS  Google Scholar 

  18. Carloni V, Romanelli RG, Pinzani M et al. Focal adhesion kinase and phospholipase C? involvement in adhesion and migration of human hepatic stellate cells. Gastroenterology 1997; 112: 522–31.

    Article  PubMed  CAS  Google Scholar 

  19. Wells A. The epidermal growth factor receptor and its ligands. In Benz S, Lui E (eds): Oncogenes. Boston: Kluwer Academic Publishers 1989; 143–68.

    Google Scholar 

  20. Aaronson SA. Growth factors and cancer. Science 1991; 254: 1146–53.

    PubMed  CAS  Google Scholar 

  21. Kim H, Turner T, Kassis J et al. EGF receptor signaling in prostate development. Histol Histopathol 1999; 14: 1175–82.

    PubMed  CAS  Google Scholar 

  22. Harris AL, Fox S, Bicknell R et al. Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer. Cancer 1994; 74: 1021–5.

    Article  PubMed  CAS  Google Scholar 

  23. Libermann TA, Nusbaum HR, Razon N et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985; 313: 144–7.

    Article  PubMed  CAS  Google Scholar 

  24. Neal DE, Marsh C, Bennett MK et al. Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours. Lancet 1985; i: 366–8.

    Article  Google Scholar 

  25. Yasui W, Sumiyoshi H, Hata J et al. Expression of epidermal growth factor receptor in human gastric and colon carcinomas. Cancer Res 1988; 48: 137–41.

    PubMed  CAS  Google Scholar 

  26. Klijn JG, Berns PM, Schmitz PI et al. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: A review on 5232 patients. Endocrine Rev 1992; 13: 3–17.

    Article  CAS  Google Scholar 

  27. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993; 53: 3579–84.

    PubMed  CAS  Google Scholar 

  28. Arteaga CL, Johnson MD, Todderud G et al. Elevated content of the tyrosine kinase substrate phospholipase C-? 1 in primary breast carcinomas. Proc Natl Acad Sci USA 1991; 88: 10435–9.

    Article  PubMed  CAS  Google Scholar 

  29. Liu D, Aguirre-Ghiso JA, Estrada Y et al. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 2002; 1: 445–57.

    Article  PubMed  CAS  Google Scholar 

  30. Ching KZ, Ramsey E, Pettigrew N et al. Expression of mRNA for epidermal growth factor, transforming growth factor-alpha and their receptor in human prostate tissue and cell lines. Mol Cell Biochem 1993; 126: 151–8.

    Article  PubMed  CAS  Google Scholar 

  31. Khoshyomn S, Penar PL, Rossi J et al. Inhibition of PLC gamma-1 activation blocks glioma cell motility and invasion of fetal rat brain aggregates. Neurosurgery 1999; 44: 568–77.

    Article  PubMed  CAS  Google Scholar 

  32. Turner T, Chen P, Goodly LJ et al. EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. Clin Exp Metastasis 1996; 14: 409–18.

    Article  PubMed  CAS  Google Scholar 

  33. Kassis J, Moellinger J, Lo H et al. A role for phospholipase C-?-mediated signaling in tumor cell invasion. Clin Cancer Res 1999; 5: 2251–60.

    PubMed  CAS  Google Scholar 

  34. Kassis J, Radinsky R, Wells A. Motility is rate-limiting for invasion of bladder carcinoma cell lines. Intern J Biochem Cell Biol 2002; 34: 262–75.

    Article  Google Scholar 

  35. Thomas SM, Coppelli FM, Song JI et al. Epidermal growth factor receptor-stimulated activation of phospholipase Cy-1 and its role in invasion of head and neck squamous cell carcinoma in vitro. ProcAm Assoc Cancer Res 2002; 43: 542–3.

    Google Scholar 

  36. Luzzi KJ, MacDonald IC, Schmidt EE et al. Multistep nature of metastatic inefficiency: Dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 1998; 153: 865–73.

    PubMed  CAS  Google Scholar 

  37. Wyckoff JB, Jones JG, Condeelis JS et al. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 2000; 60: 2504–11.

    PubMed  CAS  Google Scholar 

  38. Di Paolo G, Pellegrini L, Letinic K et al. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1? by FERM domain of talin. Nature 2002; 420: 85–9.

    Article  PubMed  CAS  Google Scholar 

  39. Gilmore AP, Burridge K. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphoshate. Nature 1996; 381: 531–5.

    Article  PubMed  CAS  Google Scholar 

  40. Chen P, Murphy-Ullrich J, Wells A. A role for gelsolin in actuating EGF receptor-mediated cell motility. J Cell Biol 1996; 134: 689–98.

    Article  PubMed  CAS  Google Scholar 

  41. Chou J, Beer-Stolz D, Burke N et al. Distribution of gelsolin and phosphoinositol 4,5-bisphosphate in lamellipodia during EGF-induced motility. Intern J Biochem Cell Biol 2002; 34: 776–90.

    Article  CAS  Google Scholar 

  42. Yu FX, Sun H-Q, Janmey PA et al. Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin. J Biol Chem 1992; 267: 14616–21.

    PubMed  CAS  Google Scholar 

  43. Aderem A. Signal transduction and the actin cytoskeleton: The roles of MARCKS and profilin. Trends Biochem Sci 1992; 17: 438–43.

    Article  PubMed  CAS  Google Scholar 

  44. Goldschmidt-Clermont PJ, Kim JW, Machesky LM et al. Regulation of phospholipase C-? 1 by profilin and tyrosine phosphorylation. Science 1991; 251: 1231–3.

    PubMed  CAS  Google Scholar 

  45. Chan AY, Bailly M, Zebda N et al. Role of cofilin in epidermal growth factor-stimulated actin polymerization and lamellipod protrusion. J Cell Biol 2000; 148: 531–42.

    Article  PubMed  CAS  Google Scholar 

  46. Chan AY, Raft S, Bailly M, et al. EGF stimulates an increase in actin nucleation and filament number at the leading edge of the lamellipod in mammary adenocarcinoma cells. J Cell Sci 1998; 111: 199–211.

    PubMed  CAS  Google Scholar 

  47. Condeelis J. How is actin polymerization nucleated in vivo? Trends Cell Biol 2001; 11: 288–93.

    Article  PubMed  CAS  Google Scholar 

  48. Abedi H, Zachary I. Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J Biol Chem 1997; 272: 15442–51.

    Article  PubMed  CAS  Google Scholar 

  49. Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177–82.

    PubMed  CAS  Google Scholar 

  50. Pollak M, Beamer W, Zhang JC. Insulin-like growth factors and prostate cancer. Cancer Metastasis Rev 1998; 17: 383–90.

    Article  PubMed  CAS  Google Scholar 

  51. Goustin AS, Leof EB, Shipley GD et al. Growth factors and cancer. Cancer Res 1986; 46: 1015–29.

    PubMed  CAS  Google Scholar 

  52. Engebraaten O, Bjerkvig R, Pedersen PH et al. Effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain-tumour biopsies in vitro. Intern J Cancer 1993; 53: 209–14.

    CAS  Google Scholar 

  53. Manos EJ, Kim M, Kassis J et al. Prostin-1, a novel phospholipase C-? regulated gene negatively associated with prostate tumor invasion. Oncogene 2001; 20: 2781–90.

    Article  PubMed  CAS  Google Scholar 

  54. Miyake H, Hara I, Yamanaka K et al. Elevation of urokinase-type plasminogen activator and its receptor densities as new predictors of disease progression and prognosis in men with prostate cancer. Intern J Oncol 1999; 14: 535–41.

    CAS  Google Scholar 

  55. Chan JM, Stampfer MJ, Giovannucci E et al. Plasma insulin-like growth factor-1 and prostate cancer risk: A prospective study. Science 1998; 279: 563–6.

    Article  PubMed  CAS  Google Scholar 

  56. Nishimura K, Kitamura M, Miura H et al. Prostate stromal cellderived hepatocyte growth factor induces invasion of prostate cancer cell line DU145 through tumor-stromal interaction. Prostate 1999; 41: 145–53.

    Article  PubMed  CAS  Google Scholar 

  57. Maeda Y, Tanaka S, Hino J et al. Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3. EMBO J 2000; 19: 2475–82.

    Article  PubMed  CAS  Google Scholar 

  58. Murphy-Ullrich J. The de-adhesive activity of matricellular proteins: Is intermediate cell adhesion an adaptive state. J Clin Invest 2001; 107: 785–90.

    Article  PubMed  CAS  Google Scholar 

  59. Ye K, Aghasi B, Luo HR et al. Phospholipase C? 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 2002; 415: 541–4.

    Article  PubMed  CAS  Google Scholar 

  60. Patterson RL, van Rossum DB, Ford DL et al. Phospholipase C-? is required for agonist-induced Ca2+ entry. Cell 2002; 111: 529–41.

    Article  PubMed  CAS  Google Scholar 

  61. Ling K, Doughman RL, Firestone AJ et al. Type I-gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature 2002, 420: 89–93.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Alan Wells.

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Wells, A., Grandis, J.R. Phospholipase C-γ1 in tumor progression. Clin Exp Metastasis 20, 285–290 (2003). https://doi.org/10.1023/A:1024088922957

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