Skip to main content

Src Kinase and Pancreatic Cancer

  • Chapter
Book cover Pancreatic Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 177))

Abstract

The c-Src non-receptor tyrosine kinase is overexpressed in a large number of human malignancies. It is linked to tumour development and progression to distant metastases by promoting cell proliferation, invasion, and motility. Recently, promising anticancer therapeutics targeting c-Src have been developed that are under clinical investigation.

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

Access this chapter

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R (2001) Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 98:7319–7324

    Article  PubMed  CAS  Google Scholar 

  2. Brown MT, Cooper AJ (1996) Regulation, substrates and functions of src. Biochim Biophys Acta 1287:121–149

    PubMed  Google Scholar 

  3. Chang JH, Gill S, Settleman J, Parsons S (1995) c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120rasGAP following epidermal growth factor stimulation. J Cell Biol 130:355–368

    Article  PubMed  CAS  Google Scholar 

  4. Cooper JA, Gould KL, Cartwright CA, et al. (1986) Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science 231:1431–1434

    Article  PubMed  CAS  Google Scholar 

  5. Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF (1993) Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor. EMBO J 12:943–950

    PubMed  CAS  Google Scholar 

  6. Czernilofsky AP, Levinson AD, Varmus HE, Bishop JM, Tischer E, Goodman HM (1980) Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product. Nature 287:198–203

    Article  PubMed  CAS  Google Scholar 

  7. DeMali KA, Godwin SL, Soltoff SP, et al. (1999) Multiple roles for Src in a PDGF-stimulated cell. Exp Cell Res 253:271–279

    Article  PubMed  CAS  Google Scholar 

  8. Duxbury MS, Ito H, Zinner MJ, et al. (2004a) Inhibition of SRC tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells. Clin Cancer Res 10:2307–2318

    Article  PubMed  CAS  Google Scholar 

  9. Duxbury MS, Ito H, Zinner MJ, et al. (2004b) siRNA directed against c-Src enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity. J Am Coll Surg 198:953–959

    Article  PubMed  Google Scholar 

  10. Frame MC (2002) Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta 1602:114–130

    PubMed  CAS  Google Scholar 

  11. Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D, Birchmeier W (1991) E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113:173–185

    Article  PubMed  CAS  Google Scholar 

  12. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 4:222–231

    Article  PubMed  CAS  Google Scholar 

  13. Golas JM, Arndt K, Etienne C, et al. (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res 63:375–381

    PubMed  CAS  Google Scholar 

  14. Golas JM, Arndt K, Etienne C, et al. (2005) SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res 65:5358–5364

    Article  PubMed  CAS  Google Scholar 

  15. Green TP, Fennel M, Whittaker R, et al. (2004) Preclinical activity of AZD0530, a novel oral potent and selective inhibitor of Src family kinases. Eur J Cancer 2:A361

    Google Scholar 

  16. Huebner RJ, Todaro GJ (1969) Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci USA 64:1087–1094

    Article  PubMed  CAS  Google Scholar 

  17. Irby RB, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ (1999) Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet 21:187–190

    Article  PubMed  CAS  Google Scholar 

  18. Ito H, Gardner-Thorpe J, Zinner MJ, et al. (2003) Inhibition of tyrosine kinase Src suppresses pancreatic cancer invasiveness. Surgery 134:221–226

    Article  PubMed  Google Scholar 

  19. Jamora C, Fuchs E (2002) Intercellular adhesion, signalling and the cytoskeleton. Nat Cell Biol 4:E101–E108

    Article  PubMed  CAS  Google Scholar 

  20. Johnson LN, Noble ME, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85:149–158

    Article  PubMed  CAS  Google Scholar 

  21. Jung EJ, Kim CW (2002) Interaction between chicken protein tyrosine phosphatase 1 (CPTP1)-like rat protein phosphatase 1 (PTP 1) and p60(v-src) in v-src transformed Rat-1 fibroblasts. Exp Mol Med 34:476–480

    PubMed  CAS  Google Scholar 

  22. Kilarski WW, Jura N, Gerwins P (2003) Inactivation of Src family kinases inhibits angiogenesis in vivo: implications for a mechanism involving organization of the actin cytoskeleton. Exp Cell Res 291:70–82

    Article  PubMed  CAS  Google Scholar 

  23. Kim M, Tezuka T, Tanaka K, et al. (2004) Cbl-c suppresses v-Src induced transformation through ubiquitin-dependent protein degradation. Oncogene 23:1645–1655

    Article  PubMed  CAS  Google Scholar 

  24. Landgren E, Blume-Jensen P, Courtneidge SA, Claesson-Welsh L (1995) Fibroblast growth factor receptor-1 regulation of Src family kinases. Oncogene 10:2027–2035

    PubMed  CAS  Google Scholar 

  25. Laukaitis CM, Webb DJ, Donais K, Horwitz AF (2001) Differential dynamics of α-actinin during formation of disassembly of adhesions in migrating cells. J Cell Biol 153:1427–1440

    Article  PubMed  CAS  Google Scholar 

  26. Lutz MP, Esser IB, Flossmann-Kast BB, et al. (1998) Overexpression and activation of the tyrosine kinase Src in human pancreatic cancer. Biochem Biophys Res Commun 243:503–508

    Article  PubMed  CAS  Google Scholar 

  27. Mori S, Rönnstrand L, Yokote K, Engström A, Courtneidge SA, Claesson-Welsh L, Heldin CH (1993) Identification of two juxtamembrane autophosphorylation sites in the PDGFβ-receptor; involvement in the interaction with Src family tyrosine kinases. EMBO J 12:2257–2264

    PubMed  CAS  Google Scholar 

  28. Muthuswamy SK, Siegel PM, Dankort DL, et al. (1994) Mammary tumors expressing the neu proto-oncogene possess elevated c-Src tyrosine kinase activity. Mol Cell Biol 14:735–743

    PubMed  CAS  Google Scholar 

  29. Nakagawa T, Tanaka S, Suzuki H, Takayanagi H, Miyazaki T, Nakamura K, Tsuruo T (2000) Overexpression of the csk gene suppresses tumor metastasis in vivo. Int J Cancer 88:384–391

    Article  PubMed  CAS  Google Scholar 

  30. Nigg EA, Sefton BM, Hunter T, et al. (1982) Immunofluorescent localization of the transforming protein of Rous sarcoma virus with antibodies against a synthetic src peptide. Proc Natl Acad Sci USA 79:5322–5326

    Article  PubMed  CAS  Google Scholar 

  31. Noritake H, Miyamori H, Goto C, et al. (1999) Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-src. Clin Exp Metastasis 17:105–110

    Article  PubMed  CAS  Google Scholar 

  32. Perl AK, Wilgenbus P, Dahl U, et al. (1998) A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392:190–193

    Article  PubMed  CAS  Google Scholar 

  33. Rous PA (1911a) Transmission of a malignant new growth by means of a cell-free filtrate. JAMA 56:198

    Google Scholar 

  34. Rous PA (1911b) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411

    Article  Google Scholar 

  35. Rubin H (1955) Quantitative relations between causative virus and cell in the Rous No. 1 chicken sarcoma. Virology 6:669–688

    Google Scholar 

  36. Sastry SK, Burridge K (2000) Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res 261:25–36

    Article  PubMed  CAS  Google Scholar 

  37. Sefton BM, Trowbridge IS, Cooper JA, Scolnick EM (1982) The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell 31:465–474

    Article  PubMed  CAS  Google Scholar 

  38. Summy JM, Gallick GE (2003) Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev 22:337–358

    Article  PubMed  CAS  Google Scholar 

  39. Summy JM, Trevino JG, Lesslie DP, et al. (2005) AP23846, a novel and highly potent Src family kinase inhibitor, reduces vascular endothelial growth factor and interleukin-8 expression in human solid tumor cell lines and abrogates downstream angiogenic processes. Mol Cancer Ther 4:1900–1911

    Article  PubMed  CAS  Google Scholar 

  40. Takeya T, Hanafusa H (1982) DNA sequence of the viral and cellular src gene of chickens. 2. Comparison of the src genes of two strains of avian sarcoma virus and of the cellular homolog. J Virol 44:12–18

    PubMed  CAS  Google Scholar 

  41. Takeya T, Feldman RA, Hanafausa H (1982) DNA sequence of the viral and cellular src gene of chickens. 1. Complete nucleotide sequence of an EcoRI fragment of recovered avian sarcoma virus which codes for gp37 and pp60src. J Virol 44:1–11

    PubMed  CAS  Google Scholar 

  42. Thomas JW, Ellis B, Boerner RJ, Knight WB, White GC, Schaller MD (1998) SH2- and SH3-mediated interactions between focal adhesion kinase and Src. J Biol Chem 273:577–583

    Article  PubMed  CAS  Google Scholar 

  43. Tice DA, Biscardi JS, Nickles AL, Parsons SJ (1999) Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci USA 96:1415–1420

    Article  PubMed  CAS  Google Scholar 

  44. Varmus HE, Quintrell N, Wyke J (1981) Revertants of an ASV-transformed rat cell line have lost the complete provirus or sustained mutations in src. Virology 108:28–46

    Article  PubMed  CAS  Google Scholar 

  45. Yamaguchi H, Hendrickson WA (1996) Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature 384:484–489

    Article  PubMed  CAS  Google Scholar 

  46. Yezhelyev MV, Koehl G, Guba M, et al. (2004) Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res 10:8028–8036

    Article  PubMed  CAS  Google Scholar 

  47. Zheng XM, Wang Y, Pallen CJ (1992) Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase. Nature 359:336–339

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hilbig, A. (2008). Src Kinase and Pancreatic Cancer. In: Pancreatic Cancer. Recent Results in Cancer Research, vol 177. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71279-4_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-71279-4_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-71266-4

  • Online ISBN: 978-3-540-71279-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics