Cancer and Metastasis Reviews

, Volume 22, Issue 4, pp 337–358 | Cite as

Src family kinases in tumor progression and metastasis

Article

Abstract

The Src family of non-receptor protein tyrosine kinases plays critical roles in a variety of cellular signal transduction pathways, regulating such diverse processes as cell division, motility, adhesion, angiogenesis, and survival. Constitutively activated variants of Src family kinases, including the viral oncoproteins v-Src and v-Yes, are capable of inducing malignant transformation of a variety of cell types. Src family kinases, most notably although not exclusively c-Src, are frequently overexpressed and/or aberrantly activated in a variety of epithelial and non-epithelial cancers. Activation is very common in colorectal and breast cancers, and somewhat less frequent in melanomas, ovarian cancer, gastric cancer, head and neck cancers, pancreatic cancer, lung cancer, brain cancers, and blood cancers. Further, the extent of increased Src family activity often correlates with malignant potential and patient survival. Activation of Src family kinases in human cancers may occur through a variety of mechanisms and is frequently a critical event in tumor progression. Exactly how Src family kinases contribute to individual tumors remains to be defined completely, however they appear to be important for multiple aspects of tumor progression, including proliferation, disruption of cell/cell contacts, migration, invasiveness, resistance to apoptosis, and angiogenesis. This review details the evidence for Src family activation in human tumors, and emphasizes possible consequences to tumor progression. Given the ability of Src and its family members to participate in so many aspects of tumor progression and metastasis, Src family kinases are attractive targets for future anti-cancer therapeutics.

Src protein tyrosine kinase tumor progression angiogenesis cell survival 

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References

  1. 1.
    Rous P: A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13: 397–411, 1911Google Scholar
  2. 2.
    Brugge JS, Erikson RL: Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269: 346–348, 1977Google Scholar
  3. 3.
    Stehelin D, Varmus HE, Bishop JM, Vogt PK: DNA related to the transformingg ene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260: 170–173, 1976Google Scholar
  4. 4.
    Hunter T, Sefton BM: Transformingg ene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77: 1311–1315, 1980Google Scholar
  5. 5.
    Thomas SM, Brugge JS: Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13: 513–609, 1997Google Scholar
  6. 6.
    Martin GS: The huntingof the Src. Nat Rev Mol Cell Biol 2: 467–475, 2001Google Scholar
  7. 7.
    Toyoshima K, Yamamoto T, Kawai S, Yoshida M: Viral oncogenes, v-yes and v-erbB, and their cellular counterparts. Adv Virus Res 32: 97–127, 1987Google Scholar
  8. 8.
    Frame MC: Src in cancer: Deregulation and consequences for cell behavior. Biochim Biophys Acta 1602: 114–130, 2002Google Scholar
  9. 9.
    Sicheri F, Moarefi I, Kuriyan J: Crystal structure of the Src family tyrosine kinase Hck. Nature 385: 602–609, 1997Google Scholar
  10. 10.
    Xu W, Harrison SC, Eck MJ: Three-dimensional structure of the tyrosine kinase c-Src. Nature 385: 595–602, 1997Google Scholar
  11. 11.
    Kmiecik TE, Shalloway D: Activation and suppression of pp60c-src transformingability by mutation of its primary sites of tyrosine phosphorylation. Cell 49: 65–73, 1987Google Scholar
  12. 12.
    Piwnica-Worms H, Saunders KB, Roberts TM, Smith AE, ChengSH: Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell 49: 75–82, 1987Google Scholar
  13. 13.
    Cartwright CA, Eckhart W, Simon S, Kaplan PL: Cell transformation by pp60c-src mutated in the carboxyterminal regulatory domain. Cell 49: 83–91, 1987Google Scholar
  14. 14.
    Irby RB, Mao W, Coppola D, KangJ, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ: ActivatingSRC mutation in a subset of advanced human colon cancers. Nat Genet 21: 187–190, 1999Google Scholar
  15. 15.
    Irby RB, Yeatman TJ: Role of Src expression and activation in human cancer. Oncogene 19: 5636–5642, 2000Google Scholar
  16. 16.
    Brown MT, Cooper JA: Regulation, substrates and functions of src. Biochim Biophys Acta 1287: 121–149, 1996Google Scholar
  17. 17.
    Fidler IJ: The biology of cancer metastasis or, ‘you cannot fix it if you do not know how it works’. Bioessays 13: 551–554, 1991Google Scholar
  18. 18.
    Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA: Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem 261: 13754–13759, 1986Google Scholar
  19. 19.
    Bolen JB, Veillette A, Schwartz AM, Deseau V, Rosen N: Analysis of pp60c-src in human colon carcinoma and normal human colon mucosal cells. Oncogene Res 1: 149–168, 1987Google Scholar
  20. 20.
    Cartwright CA, Kamps MP, Meisler AI, Pipas JM, Eckhart W: pp60c-src activation in human colon carcinoma. J Clin Invest 83: 2025–2033, 1989Google Scholar
  21. 21.
    Cartwright CA, Meisler AI, Eckhart W: Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis. Proc Natl Acad Sci USA 87: 558–562, 1990Google Scholar
  22. 22.
    Cartwright CA, Coad CA, Egbert BM: Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis. J Clin Invest 93: 509–515, 1994Google Scholar
  23. 23.
    Weber TK, Steele G, Summerhayes IC: Differential pp60c-src activity in well and poorly differentiated human colon carcinomas and cell lines. J Clin Invest 90: 815–821, 1992Google Scholar
  24. 24.
    Talamonti MS, Roh MS, Curley SA, Gallick GE: Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer. J Clin Invest 91: 53–60, 1993Google Scholar
  25. 25.
    Termuhlen PM, Curley SA, Talamonti MS, Saboorian MH, Gallick GE: Site-specific differences in pp60c-src activity in human colorectal metastases. J SurgRes 54: 293–298, 1993Google Scholar
  26. 26.
    Sakai T, Kawakatsu H, Fujita M, Yano J, Owada MK: An epitope localized in c-Src negative regulatory domain is a potential marker in early stage of colonic neoplasms. Lab Invest 78: 219–225, 1998Google Scholar
  27. 27.
    Iravani S, Mao W, Fu L, Karl R, Yeatman T, Jove R, Coppola D: Elevated c-Src protein expression is an early event in colonic neoplasia. Lab Invest 78: 365–371, 1998Google Scholar
  28. 28.
    Aligayer H, Boyd DD, Heiss MM, Abdalla EK, Curley SA, Gallick GE: Activation of Src kinase in primary colorectal carcinoma: An indicator of poor clinical prognosis. Cancer 94: 344–351, 2002Google Scholar
  29. 29.
    Park J, Meisler AI, Cartwright CA: c-Yes tyrosine kinase activity in human colon carcinoma. Oncogene 8: 2627–2635, 1993Google Scholar
  30. 30.
    Pena SV, Melhem MF, Meisler AI, Cartwright CA: Elevated c-yes tyrosine kinase activity in premalignant lesions of the colon. Gastroenterology 108: 117–124, 1995Google Scholar
  31. 31.
    Alexander RJ, Panja A, Kaplan-Liss E, Mayer L, Raicht RF: Expression of protooncogene-encoded mRNA by colonic epithelial cells in inflammatory bowel disease. Dig Dis Sci 41: 660–669, 1996Google Scholar
  32. 32.
    Han NM, Curley SA, Gallick GE: Differential activation of pp60(c-src) and pp62(c-yes) in human colorectal carcinoma liver metastases. Clin Cancer Res 2: 1397–1404, 1996Google Scholar
  33. 33.
    Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR: Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest 90: 1622–1627, 1992Google Scholar
  34. 34.
    Ignelzi MA, Jr., Miller DR, Soriano P, Maness PF: Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1. Neuron 12: 873–884, 1994Google Scholar
  35. 35.
    Kaplan KB, Swedlow JR, Morgan DO, Varmus HE: c-Src enhances the spreadingof src-/-fibroblasts on fibronectin by a kinase-independent mechanism. Genes Dev 9: 1505–1517, 1995Google Scholar
  36. 36.
    Hall CL, Lange LA, Prober DA, Zhang S, Turley EA: pp60(c-src) is required for cell locomotion regulated by the hyaluronanreceptor RHAMM. Oncogene 13: 2213–2224, 1996Google Scholar
  37. 37.
    Veillette A, Foss FM, Sausville EA, Bolen JB, Rosen N: Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. Oncogene Res 1: 357–374, 1987Google Scholar
  38. 38.
    Muise-Helmericks RC, Rosen N: Identification of a novel repressive element in the proximal lck promoter. J Biol Chem 270: 27538–27543, 1995Google Scholar
  39. 39.
    Irby R, Mao W, Coppola D, Jove R, Gamero A, Cuthbertson D, Fujita DJ, Yeatman TJ: Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. Cell Growth Differ 8: 1287–1295, 1997Google Scholar
  40. 40.
    Pories SE, Hess DT, Swenson K, Lotz M, Moussa R, Steele G, Jr., Shibata D, Rieger-Christ KM, Summerhayes C: Overexpression of pp60c-src elicits invasive behavior in rat colon epithelial cells. Gastroenterology 114: 1287–1295, 1998Google Scholar
  41. 41.
    Garcia R, Parikh NU, Saya H, Gallick GE: Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines. Oncogene 6: 1983–1989, 1991Google Scholar
  42. 42.
    Kawai N, Tsuji S, Tsujii M, Ito T, Yasumaru M, Kakiuchi Y, Kimura A, Komori M, Sasaki Y, Hayashi N, Kawano S, Dubois R, Hori M: Tumor necrosis factor alpha stimulates invasion of Src-activated intestinal cells. Gastroenterology 122: 331–339, 2002Google Scholar
  43. 43.
    Novotny-Smith CL, Gallick GE: Growth inhibition of human colorectal carcinoma cell lines by tumor necrosis factor-alpha correlates with reduced activity of pp60c-src. J Immunother 11: 159–168, 1992Google Scholar
  44. 44.
    Nakagawa T, Tanaka S, Suzuki H, Takayanagi H, Miyazaki T, Nakamura K, Tsuruo T: Overexpression of the csk gene suppresses tumor metastasis in vivo. Int J Cancer 88: 384–391, 2000Google Scholar
  45. 45.
    Boyer B, Bourgeois Y, Poupon MF: Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene 21: 2347–2356, 2002Google Scholar
  46. 46.
    Staley CA, Parikh NU, Gallick GE: Decreased tumorigenicity of a human colon adenocarcinoma cell line by an antisense expression vector specific for c-Src. Cell Growth Differ 8: 269–274, 1997Google Scholar
  47. 47.
    Di Domenico M, Castoria G, Bilancio A, Migliaccio A, Auricchio F: Estradiol activation of human colon carcinoma-derived Caco-2 cell growth. Cancer Res 56: 4516–4521, 1996Google Scholar
  48. 48.
    Mao W, Irby R, Coppola D, Fu L, Wloch M, Turner J, Yu H, Garcia R, Jove R, Yeatman TJ: Activation of c-Src by receptor tyrosine kinases in human colon cancer cells Src family kinases in tumor progression and metastasis 353 with high metastatic potential. Oncogene 15: 3083–3090, 1997Google Scholar
  49. 49.
    DeSeau V, Rosen N, Bolen JB: Analysis of pp60c-src tyrosine kinase activity and phosphotyrosyl phosphatase activity in human colon carcinoma and normal human colon mucosal cells. J Cell Biochem 35: 113–128, 1987Google Scholar
  50. 50.
    Park J, Cartwright CA: Src activity increases and Yes activity decreases duringmitosis of human colon carcinoma cells. Mol Cell Biol 15: 2374–2382, 1995Google Scholar
  51. 51.
    Peng ZY, Cartwright CA: Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular association. Oncogene 11: 1955–1962, 1995Google Scholar
  52. 52.
    Zheng XM, Resnick RJ, Shalloway D: A phosphotyrosine displacement mechanism for activation of Src by PTPalpha. Embo J 19: 964–978, 2000Google Scholar
  53. 53.
    Cam WR, Masaki T, Shiratori Y, Kato N, Ikenoue T, Okamoto M, Igarashi K, Sano T, Omata M: Reduced Cterminal Src kinase activity is correlated inversely with pp60(c-src) activity in colorectal carcinoma. Cancer 92: 61–70, 2001Google Scholar
  54. 54.
    Daigo Y, Furukawa Y, Kawasoe T, Ishiguro H, Fujita M, Sugai S, Nakamori S, Liefers GJ, Tollenaar RA, van de Velde CJ, Nakamura Y: Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients. Cancer Res 59: 4222–4224, 1999Google Scholar
  55. 55.
    Nilbert M, Fernebro E: Lack of activating c-SRC mutations at codon 531 in rectal cancer. Cancer Genet Cytogenet 121: 94–95, 2000Google Scholar
  56. 56.
    Wang NM, Yeh KT, Tsai CH, Chen SJ, Chang JG: No evidence of correlation between mutation at codon 531 of src and the risk of colon cancer in Chinese. Cancer Lett 150: 201–204, 2000Google Scholar
  57. 57.
    Rajala RV, Dehm S, Bi X, Bonham K, Sharma RK: Expression of N-myristoyltransferase inhibitor protein and its relationship to c-Src levels in human colon cancer cell lines. Biochem Biophys Res Commun 273: 1116–1120, 2000Google Scholar
  58. 58.
    Brunton VG, Ozanne BW, Paraskeva C, Frame MC: A role for epidermal growth factor receptor, c-Src and focal adhesion kinase in an in vitro model for the progression of colon cancer. Oncogene 14: 283–293, 1997Google Scholar
  59. 59.
    Allgayer H, Wang H, Gallick GE, Crabtree A, Mazar A, Jones T, Kraker AJ, Boyd DD: Transcriptional induction of the urokinase receptor gene by a constitutively active Src. Requirement of an upstream motif (-152/-135) bound with Sp1. J Biol Chem 274: 18428–18437, 1999Google Scholar
  60. 60.
    Owens DW, McLean GW, Wyke AW, Paraskeva C, Parkinson EK, Frame MC, Brunton VG: The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell-cell contacts. Mol Biol Cell 11: 51–64, 2000Google Scholar
  61. 61.
    Irby RB, Yeatman TJ: Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells. Cancer Res 62: 2669–2674, 2002Google Scholar
  62. 62.
    Avizienyte E, Wyke AW, Jones RJ, McLean GW, Westhoff MA, Brunton VG, Frame MC: Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signaling. Nat Cell Biol 4: 632–638, 2002Google Scholar
  63. 63.
    Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP: Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 375: 577–581, 1995Google Scholar
  64. 64.
    Fleming RY, Ellis LM, Parikh NU, Liu W, Staley CA, Gallick GE: Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by activity of src kinase. Surgery 122: 501–507, 1997Google Scholar
  65. 65.
    Ellis LM, Staley CA, Liu W, Fleming RY, Parikh NU, Bucana CD, Gallick GE: Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src. J Biol Chem 273: 1052–1057, 1998Google Scholar
  66. 66.
    Malek RL, Irby RB, Guo QM, Lee K, Wong S, He M, Tsai J, Frank B, Liu ET, Quackenbush J, Jove R, Yeatman TJ, Lee NH: Identification of Src transformation fingerprint in human colon cancer. Oncogene 21: 7256–7265, 2002Google Scholar
  67. 67.
    Jacobs C, Rubsamen H: Expression of pp60c-src protein kinase in adult and fetal human tissue: High activities in some sarcomas and mammary carcinomas. Cancer Res 43: 1696–1702, 1983Google Scholar
  68. 68.
    Lehrer S, O'shaughnessy J, Song HK, Levine E, Savoretti P, Dalton J, Lipsztein R, Kalnicki S, Bloomer WD: Activity of pp60c-src protein kinase in human breast cancer. Mt Sinai J Med 56: 83–85, 1989Google Scholar
  69. 69.
    Koster A, Landgraf S, Leipold A, Sachse R, Gebhart E, Tulusan AH, Ronay G, Schmidt C, Dingermann T: Expression of oncogenes in human breast cancer specimens. Anticancer Res 11: 193–201, 1991Google Scholar
  70. 70.
    Ottenhoff-Kalff AE, Rijksen G, van Beurden EA, Hennipman A, Michels AA, Staal GE: Characterization of protein tyrosine kinases from human breast cancer: Involvement of the c-src oncogene product. Cancer Res 52: 4773–4778, 1992Google Scholar
  71. 71.
    Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A, Rijksen G: c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol 180: 383–388, 1996Google Scholar
  72. 72.
    Reissig D, Clement J, Sanger J, Berndt A, Kosmehl H, Bohmer FD: Elevated activity and expression of Srcfamily kinases in human breast carcinoma tissue versus matched non-tumor tissue. J Cancer Res Clin Oncol 127: 226–230, 2001Google Scholar
  73. 73.
    Biscardi JS, Ishizawar RC, Silva CM, Parsons SJ: Tyrosine kinase signaling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res 2: 203–210, 2000Google Scholar
  74. 74.
    Alonso G, Koegl M, Mazurenko N, Courtneidge SA: Sequence requirements for binding of Src family tyrosine kinases to activated growth factor receptors. J Biol Chem 270: 9840–9848, 1995Google Scholar
  75. 75.
    Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF: Activation of Src family kinases by colony stimulatingfactor-1, and their association with its receptor. Embo J 12: 943–950, 1993Google Scholar
  76. 76.
    Kypta RM, Goldberg Y, Ulug ET, Courtneidge SA: Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62: 481–492, 1990Google Scholar
  77. 77.
    Mori S, Ronnstrand L, Yokote K, Engstrom A, Courtneidge SA, Claesson-Welsh L, Heldin CH: Identification of two juxtamembrane autophosphorylation sites in the PDGF beta-receptor; involvement in the interaction with Src family tyrosine kinases. Embo J 12: 2257–2264, 1993Google Scholar
  78. 78.
    Twamley GM, Kypta RM, Hall B, Courtneidge SA: Association of Fyn with the activated platelet-derived growth factor receptor: Requirements for binding and phosphorylation. Oncogene 7: 1893–1901, 1992Google Scholar
  79. 79.
    Luttrell DK, Lee A, Lansing TJ, Crosby RM, Jung KD, Willard D, Luther M, Rodriguez M, Berman J, Gilmer TM: Involvement of pp60c-src with two major signaling pathways in human breast cancer. Proc Natl Acad Sci USA 91: 83–87, 1994Google Scholar
  80. 80.
    Oude Weernink PA, Ottenhoff-Kalff AE, Vendrig MP, van Beurden EA, Staal GE, Rijksen G: Functional interaction between the epidermal growth factor receptor and c-Src kinase activity. FEBS Lett 352: 296–300, 1994Google Scholar
  81. 81.
    Muthuswamy SK, Muller WJ: Activation of the Src family of tyrosine kinases in mammary tumorigenesis. Adv Cancer Res 64: 111–123, 1994Google Scholar
  82. 82.
    Muthuswamy SK, Siegel PM, Dankort DL, Webster MA, Muller WJ: Mammary tumors expressing the neu proto-oncogene possess elevated c-Src tyrosine kinase activity. Mol Cell Biol 14: 735–743, 1994Google Scholar
  83. 83.
    Muthuswamy SK, Muller WJ: Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor. Oncogene 11: 271–279, 1995Google Scholar
  84. 84.
    Muthuswamy SK, Muller WJ: Activation of Src family kinases in Neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo. Oncogene 11: 1801–1810, 1995Google Scholar
  85. 85.
    Biscardi JS, Belsches AP, Parsons SJ: Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells. Mol Carcinog 21: 261–272, 1998Google Scholar
  86. 86.
    Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL, 3rd, Kufe D: The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. J Biol Chem 276: 35239–35242, 2001Google Scholar
  87. 87.
    Egan C, Pang A, Durda D, Cheng HC, Wang JH, Fujita DJ: Activation of Src in human breast tumor cell lines: Elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530. Oncogene 18: 1227–1237, 1999Google Scholar
  88. 88.
    Bjorge JD, Pang A, Fujita DJ: Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylatingand activating c-Src in several human breast cancer cell lines. J Biol Chem 275: 41439–41446, 2000Google Scholar
  89. 89.
    Webster MA, Cardiff RD, Muller WJ: Induction of mammary epithelial hyperplasias and mammary tumors in transgenic mice expressing a murine mammary tumor virus/activated c-src fusion gene. Proc Natl Acad Sci USA 92: 7849–7853, 1995Google Scholar
  90. 90.
    Guy CT, Muthuswamy SK, Cardiff RD, Soriano P, Muller WJ: Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev 8: 23–32, 1994Google Scholar
  91. 91.
    Arnold SF, Obourn JD, Jaffe H, Notides AC: Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol 9: 24–33, 1995Google Scholar
  92. 92.
    Arnold SF, Vorojeikina DP, Notides AC: Phosphorylation of tyrosine 537 on the human estrogen receptor is required for bindingto an estrogen response element. J Biol Chem 270: 30205–30212, 1995Google Scholar
  93. 93.
    Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F: Tyrosine kinase/ p21ras/MAP-kinase pathway activation by estradiolreceptor complex in MCF-7 cells. Embo J 15: 1292–1300, 1996Google Scholar
  94. 94.
    Migliaccio A, Piccolo D, Castoria G, Di Domenico M, Bilancio A, Lombardi M, Gong W, Beato M, Auricchio F: Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor. Embo J 17: 2008–2018, 1998Google Scholar
  95. 95.
    Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT, Edwards DP: Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol Cell 8: 269–280, 2001Google Scholar
  96. 96.
    Castoria G, Migliaccio A, Bilancio A, Di Domenico M, de Falco A, Lombardi M, Fiorentino R, Varricchio L, Barone MV, Auricchio F: PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. Embo J 20: 6050–6059, 2001Google Scholar
  97. 97.
    Tsai EM, Wang SC, Lee JN, Hung MC: Akt activation by estrogen in estrogen receptor-negative breast cancer cells. Cancer Res 61: 8390–8392, 2001Google Scholar
  98. 98.
    Maa MC, Leu TH, McCarley DJ, Schatzman RC, Parsons SJ: Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: Implications for the etiology of multiple human cancers. Proc Natl Acad Sci USA 92: 6981–6985, 1995Google Scholar
  99. 99.
    Sheffield LG: C-Src activation by ErbB2 leads to attachment-independent growth of human breast epithelial cells. Biochem Biophys Res Commun 250: 27–31, 1998Google Scholar
  100. 100.
    Amundadottir LT, Leder P: Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. Oncogene 16: 737–746, 1998Google Scholar
  101. 101.
    Vercoutter-Edouart A, Lemoine J, Smart CE, Nurcombe V, Boilly B, Peyrat J, Hondermarck H: The mitogenic signaling pathway for fibroblast growth factor-2 involves the tyrosine phosphorylation of cyclin D2 in MCF-7 human breast cancer cells. FEBS Lett 478: 209–215, 2000Google Scholar
  102. 102.
    Belsches-Jablonski AP, Biscardi JS, Peavy DR, Tice DA, Romney DA, Parsons SJ: Src family kinases and HER2 interactions in human breast cancer cell growth and survival. Oncogene 20: 1465–1475, 2001Google Scholar
  103. 103.
    Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N: Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res 59: 6145–6152, 1999Google Scholar
  104. 104.
    Hung W, Elliott B: Co-operative effect of c-Src tyrosine kinase and Stat3 in activation of hepatocyte growth factor expression in mammary carcinoma cells. J Biol Chem 276: 12395–12403, 2001Google Scholar
  105. 105.
    Maulik G, Shrikhande A, Kijima T, Ma PC, Morrison PT, Salgia R: Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev 13: 41–59, 2002Google Scholar
  106. 106.
    Garcia R, Bowman TL, Niu G, Yu H, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S, Laudano A, Gazit A, Levitzki A, Kraker A, Jove R: Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20: 2499–2513, 2001Google Scholar
  107. 107.
    Olayioye MA, Badache A, Daly JM, Hynes NE: An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway. Exp Cell Res 267: 81–87, 2001Google Scholar
  108. 108.
    Bougeret C, Jiang S, Keydar I, Avraham H: Functional analysis of Csk and CHK kinases in breast cancer cells. J Biol Chem 276: 33711–33720, 2001Google Scholar
  109. 109.
    McShan GD, Zagozdzon R, Park SY, Zrihan-Licht S, Fu Y, Avraham S, Avraham H: Csk homologous kinase associates with RAFTK/Pyk2 in breast cancer cells and negatively regulates its activation and breast cancer cell migration. Int J Oncol 21: 197–205, 2002Google Scholar
  110. 110.
    Pal S, Datta K, Mukhopadhyay D: Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res 61: 6952–6957, 2001Google Scholar
  111. 111.
    Hall CL, Turley EA: Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. J Neurooncol 26: 221–229, 1995Google Scholar
  112. 112.
    Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H: RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion. Oncogene 19: 1318–1328, 2000Google Scholar
  113. 113.
    Gutwein P, Oleszewski M, Mechtersheimer S, Agmon-Levin N, Krauss K, Altevogt P: Role of Src kinases in the ADAM-mediated release of L1 adhesion molecule from human tumor cells. J Biol Chem 275: 15490–15497, 2000Google Scholar
  114. 114.
    Rahimi N, Hung W, Tremblay E, Saulnier R, Elliott B: c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells. J Biol Chem 273: 33714–33721, 1998Google Scholar
  115. 115.
    Nam JS, Ino Y, Sakamoto M, Hirohashi S: Src family kinase inhibitor PP2 restores the E-Cadherin/Catenin cell adhesion system in human cancer cells and reduces cancer metastasis. Clin Cancer Res 8: 2430–2436, 2002Google Scholar
  116. 116.
    Lee HJ, Kim E, Jee B, Hahn JH, Han K, JungKC, Park SH, Lee H: Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells. Exp Mol Med 34: 177–183, 2002Google Scholar
  117. 117.
    Loganzo F Jr., Dosik JS, Zhao Y, Vidal MJ, Nanus DM, Sudol M, Albino AP: Elevated expression of protein tyrosine kinase c-Yes, but not c-Src, in human malignant melanoma. Oncogene 8: 2637–2644, 1993Google Scholar
  118. 118.
    Marchetti D, Parikh N, Sudol M, Gallick GE: Stimulation of the protein tyrosine kinase c-Yes but not c-Src by neurotrophins in human brain-metastatic melanoma cells. Oncogene 16: 3253–3260, 1998Google Scholar
  119. 119.
    Visser CJ, Rijksen G, Woutersen RA, De Weger RA: Increased immunoreactivity and protein tyrosine kinase activity of the protooncogene pp60c-src in preneoplastic lesions in rat pancreas. Lab Invest 74: 2–11, 1996Google Scholar
  120. 120.
    Lutz MP, Esser IB, Flossmann-Kast BB, Vogelmann R, Luhrs H, Friess H, Buchler MW, Adler G: Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem Biophys Res Commun 243: 503–508, 1998Google Scholar
  121. 121.
    MacMillan-Crow LA, Greendorfer JS, Vickers SM, Thompson JA: Tyrosine nitration of c-SRC tyrosine kinase in human pancreatic ductal adenocarcinoma. Arch Biochem Biophys 377: 350–356, 2000Google Scholar
  122. 122.
    Flossmann-Kast BB, Jehle PM, Hoeflich A, Adler G, Lutz MP: Src stimulates insulin-like growth factor I (IGF-I)-dependent cell proliferation by increasingIGF-I receptor number in human pancreatic carcinoma cells. Cancer Res 58: 3551–3554, 1998Google Scholar
  123. 123.
    Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH, Testa JR: AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res 61: 589–593, 2001Google Scholar
  124. 124.
    Menke A, Philippi C, Vogelmann R, Seidel B, Lutz MP, Adler G, Wedlich D: Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines. Cancer Res 61: 3508–3517, 2001Google Scholar
  125. 125.
    Wiener JR, Nakano K, Kruzelock RP, Bucana CD, Bast RC Jr., Gallick GE: Decreased Src tyrosine kinase activity inhibits malignant human ovarian cancer tumor growth in a nude mouse model. Clin Cancer Res 5: 2164–2170, 1999Google Scholar
  126. 126.
    Venkatakrishnan G, Salgia R, Groopman JE: Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells. J Biol Chem 275: 6868–6875, 2000Google Scholar
  127. 127.
    Bourguignon LY, Zhu H, Shao L, Chen YW: CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. J Biol Chem 276: 7327–7336, 2001Google Scholar
  128. 128.
    Fanning P, Bulovas K, Saini KS, Libertino JA, Joyce AD, Summerhayes IC: Elevated expression of pp60c-src in low grade human bladder carcinoma. Cancer Res 52: 1457–1462, 1992Google Scholar
  129. 129.
    Rodier JM, Valles AM, Denoyelle M, Thiery JP, Boyer B: pp60c-src is a positive regulator of growth factor-induced cell scatteringin a rat bladder carcinoma cell line. J Cell Biol 131: 761–773, 1995Google Scholar
  130. 130.
    Cattan N, Rochet N, Mazeau C, Zanghellini E, Mari B, Chauzy C, Stora de Novion H, Amiel J, Lagrange JL, Rossi B, Gioanni J: Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scatteringand epithelial to mesenchyme transition induced by growth factors. Br J Cancer 85: 1412–1417, 2001Google Scholar
  131. 131.
    Takekura N, Yasui W, Yoshida K, Tsujino T, Nakayama H, Kameda T, Yokozaki H, Nishimura Y, Ito H, Tahara E: pp60c-src protein kinase activity in human gastric carcinomas. Int J Cancer 45: 847–851, 1990Google Scholar
  132. 132.
    Jankowski J, Coghill G, Hopwood D, Wormsley KG: Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus. Gut 33: 1033–1038, 1992Google Scholar
  133. 133.
    Kumble S, Omary MB, Cartwright CA, Triadafilopoulos G: Src activation in malignant and premalignant epithelia of Barrett's esophagus. Gastroenterology 112: 348–356, 1997Google Scholar
  134. 134.
    van Oijen MG, Rijksen G, ten Broek FW, Slootweg PJ: Overexpression of c-Src in areas of hyperproliferation in head and neck cancer, premalignant lesions and benign mucosal disorders. J Oral Pathol Med 27: 147–152, 1998Google Scholar
  135. 135.
    Kiefer PE, Wegmann B, Bacher M, Erbil C, Heidtmann H, Havemann K: Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines. J Cancer Res Clin Oncol 116: 29–37, 1990Google Scholar
  136. 136.
    Mazurenko NN, Kogan EA, Zborovskaya IB, Kisseljov FL: Expression of pp60c-src in human small cell and nonsmall cell lungcarcinomas. Eur J Cancer 28: 372–377, 1992Google Scholar
  137. 137.
    Budde RJ, Ke S, Levin VA: Activity of pp60c-src in 60 different cell lines derived from human tumors. Cancer Biochem Biophys 14: 171–175, 1994Google Scholar
  138. 138.
    Krystal GW, DeBerry CS, Linnekin D, Litz J: Lck associates with and is activated by Kit in a small cell lung cancer cell line: Inhibition of SCF-mediated growth by the Src family kinase inhibitor PP1. Cancer Res 58: 4660–4666, 1998Google Scholar
  139. 139.
    Bondzi C, Litz J, Dent P, Krystal GW: Src family kinase activity is required for Kit-mediated mitogen-activated protein (MAP) kinase activation, however loss of functional retinoblastoma protein makes MAP kinase activation unnecessary for growth of small cell lung cancer cells. Cell Growth Differ 11: 305–314, 2000Google Scholar
  140. 140.
    Sato M, Tanaka T, Maeno T, Sando Y, Suga T, Maeno Y, Sato H, Nagai R, Kurabayashi M: Inducible expression of endothelial PAS domain protein-1 by hypoxia in human lungadenocarc inoma A549 cells. Role of Src family kinases-dependent pathway. Am J Respir Cell Mol Biol 26: 127–134, 2002Google Scholar
  141. 141.
    Takenaka N, Mikoshiba K, Takamatsu K, Tsukada Y, Ohtani M, Toya S: Immunohistochemical detection of the gene product of Rous sarcoma virus in human brain tumors. Brain Res 337: 201–207, 1985Google Scholar
  142. 142.
    Bolen JB, Rosen N, Israel MA: Increased pp60c-src tyrosyl kinase activity in human neuroblastomas is associated with amino-terminal tyrosine phosphorylation of the src gene product. Proc Natl Acad Sci USA 82: 7275–7279, 1985Google Scholar
  143. 143.
    O'shaughnessy J, Deseau V, Amini S, Rosen N, Bolen JB: Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells. Oncogene Res 2: 1–18, 1987Google Scholar
  144. 144.
    Mellstrom K, Bjelfman C, Hammerling U, Pahlman S: Expression of c-src in cultured human neuroblastoma and small-cell lungcarcinom a cell lines correlates with neurocrine differentiation. Mol Cell Biol 7: 4178–4184, 1987Google Scholar
  145. 145.
    Pahlman S, Hammerling U: Src expression in small-cell lungcarcinoma and other neuroendocrine malignancies. Am Rev Respir Dis 142: S54–56, 1990Google Scholar
  146. 146.
    Bjelfman C, Hedborg F, Johansson I, Nordenskjold M, Pahlman S: Expression of the neuronal form of pp60c-src in neuroblastoma in relation to clinical stage and prognosis. Cancer Res 50: 6908–6914, 1990Google Scholar
  147. 147.
    Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A: Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene 14: 2005–2013, 1997Google Scholar
  148. 148.
    Theurillat JP, Hainfellner J, Maddalena A, Weissenberger J, Aguzzi A: Early induction of angiogenetic signals in gliomas of GFAP-v-src transgenic mice. Am J Pathol 154: 581–590, 1999Google Scholar
  149. 149.
    Hecker TP, Grammer JR, Gillespie GY, Stewart J Jr., Gladson CL: Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples. Cancer Res 62: 2699–2707, 2002Google Scholar
  150. 150.
    Torigoe T, O'Connor R, Santoli D, Reed JC: Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines. Blood 80: 617–624, 1992Google Scholar
  151. 151.
    Hallek M, Neumann C, Schaffer M, Danhauser-Riedl S, von Bubnoff N, de Vos G, Druker BJ, Yasukawa K, Griffin JD, Emmerich B: Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines. Exp Hematol 25: 1367–1377, 1997Google Scholar
  152. 152.
    Ishikawa H, Tsuyama N, Abroun S, Liu S, Li FJ, Taniguchi O, Kawano MM: Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6. Blood 99: 2172–2178, 2002Google Scholar
  153. 153.
    Choi SH, Yamanashi Y, Shiota M, Takanashi M, Hojo I, Itoh T, Watanabe T, Yamamoto T, Mori S: Expression of Lyn protein on human malignant lymphomas. Lab Invest 69: 736–742, 1993Google Scholar
  154. 154.
    Myers DE, Jun X, Waddick KG, Forsyth C, Chelstrom LM, Gunther RL, Tumer NE, Bolen J, Uckun FM: Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1–2-independent regulator of apoptosis in human B-lineage lymphoma cells. Proc Natl Acad Sci USA 92: 9575–9579, 1995Google Scholar
  155. 155.
    Holland J, Owens T: Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma Src family kinases in tumor progression and metastasis 357 line. The activation of Lyn tyrosine kinase and the mitogen-activated protein kinase pathway. J Biol Chem 272: 9108–9112, 1997Google Scholar
  156. 156.
    Katagiri K, Yokoyama KK, Yamamoto T, Omura S, Irie S, Katagiri T: Lyn and Fgr protein-tyrosine kinases prevent apoptosis duringretinoic acid-induced granulocytic differentiation of HL-60 cells. J Biol Chem 271: 11557–11562, 1996Google Scholar
  157. 157.
    Roginskaya V, Zuo S, Caudell E, Nambudiri G, Kraker AJ, Corey SJ: Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia 13: 855–861, 1999Google Scholar
  158. 158.
    Tilbrook PA, Palmer GA, Bittorf T, McCarthy DJ, Wright MJ, Sarna MK, Linnekin D, Cull VS, Williams JH, Ingley E, Schneider-Mergener J, Krystal G, Klinken SP: Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn. Cancer Res 61: 2453–2458, 2001Google Scholar
  159. 159.
    Ptasznik A, Urbanowska E, Chinta S, Costa MA, Katz BA, Stanislaus MA, Demir G, Linnekin D, Pan ZK, Gewirtz AM: Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J Exp Med 196: 667–678, 2002Google Scholar
  160. 160.
    Lionberger JM, Wilson MB, Smithgall TE: Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J Biol Chem 275: 18581–18585, 2000Google Scholar
  161. 161.
    Penninger JM, Wallace VA, Kishihara K, Mak TW: The role of p56lck and p59fyn tyrosine kinases and CD45 protein tyrosine phosphatase in T-cell development and clonal selection. Immunol Rev 135: 183–214, 1993Google Scholar
  162. 162.
    Perlmutter RM: Control of T cell development by nonreceptor protein tyrosine kinases. Cancer Surv 22: 85–95, 1995Google Scholar
  163. 163.
    Sefton BM: The lck tyrosine protein kinase. Oncogene 6: 683–686, 1991Google Scholar
  164. 164.
    Sefton BM, Taddie JA: Role of tyrosine kinases in lymphocyte activation. Curr Opin Immunol 6: 372–379, 1994Google Scholar
  165. 165.
    Abts H, Jucker M, Diehl V, Tesch H: Human chronic lymphocytic leukemia cells regularly express mRNAs of the protooncogenes lck and c-fgr. Leuk Res 15: 987–997, 1991Google Scholar
  166. 166.
    Waddick KG, Chae HP, Tuel-Ahlgren L, Jarvis LJ, Dibirdik I, Myers DE, Uckun FM: Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis. Radiat Res 136: 313–319, 1993Google Scholar
  167. 167.
    Miyazaki T, Liu ZJ, Taniguchi T: Selective cooperation of HTLV-1-encoded p40tax-1 with cellular oncoproteins in the induction of hematopoietic cell proliferation. Oncogene 12: 2403–2408, 1996Google Scholar
  168. 168.
    Majolini MB, D'Elios MM, Galieni P, Boncristiano M, Lauria F, Del Prete G, Telford JL, Baldari CT: Expression of the T-cell-specific tyrosine kinase Lck in normal B-1 cells and in chronic lymphocytic leukemia B cells. Blood 91: 3390–3396, 1998Google Scholar
  169. 169.
    Metcalf CA III, van Schravendijk MR, Dalgarno DC, Sawyer TK: Targeting protein kinases for bone disease: Discovery and development of SRC inhibitors. Curr Pharm Des 8: 2049–2075, 2002Google Scholar
  170. 170.
    Windham TC, Parikh NU, Siwak DR, Summy JM, McConkey DJ, Kraker AJ, Gallick GE: Src activation regulates anoikis in human colon tumor cell lines. Oncogene 21: 7797–7807, 2002Google Scholar
  171. 171.
    Donato NJ, Wu JY, Stapley J, Gallick G, Lin H, Arlinghaus R, Talpaz M: BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 101: 690–698, 2003Google Scholar

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© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Department of Cancer BiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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