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Integrins and prostate cancer metastases

  • Chapter
Prostate Cancer: New Horizons in Research and Treatment

Part of the book series: Developments in Oncology ((DION,volume 81))

  • 133 Accesses

Abstract

Integrins have emerged as modulators of a variety of cellular functions. They have been implicated in cell migration, survival, normal and aberrant cellular growth, differentiation, gene expression, and modulation of intracellular signal transduction pathways.

In this review article, the structural and functional characteristics of integrins, their expression and their potential role in prostate cancer metastases will be discussed.

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References

  1. Hynes RO: Cell adhesion: Old and new questions. Trends Cell Biol 9: M33–M37, 1999

    Article  PubMed  CAS  Google Scholar 

  2. Ruoslahti E: Integrins as signaling molecules and targets for tumor therapy. Kidney Int 51: 1413–1417, 1997

    Article  PubMed  CAS  Google Scholar 

  3. Byzova TV, Rabbani R, D’Souza SE, Plow EF: Role of integrin αvβ3 in vascular biology. Thromb Haemost 80: 726–734, 1998

    PubMed  CAS  Google Scholar 

  4. Zheng DQ, Woodard AS, Tallini G, Languino LR: Substrate specificity of αvβ3 integrin-mediated cell migration and PI 3-kinase/AKT pathway activation. J Biol Chem 275: 24565–24574, 2000

    Article  PubMed  CAS  Google Scholar 

  5. Hemler ME, Weitzman JB, Pasqualini R, Kawaguchi S, Kassner PD, Berdichevsky FB: Structure, biochemical properties, and biological functions of integrin cytoplasmic domains. In: Takada Y (ed) Integrins: The Biological Problems. CRC Press Inc., Boca Raton, 1995, pp 1–35

    Google Scholar 

  6. Fornaro M, Languino LR: Alternatively spliced variants: A new view of the integrin cytoplasmic domain. Matrix Biol 16: 185–193, 1997

    Article  PubMed  CAS  Google Scholar 

  7. Williams MJ, Hughes PE, O’Toole TE, Ginsberg MH: The inner world of cell adhesion: Integrin cytoplasmic domains. Trends Cell Biol 4: 109–112, 1994

    Article  PubMed  CAS  Google Scholar 

  8. Vidal F, Aberdam D, Miquel C, Christiano AM, Pulkkinen L, Uitto J, Ortonne J-P, Menegnzzi G: Integrin β4 mutations associated with junctional epidermolysis bullosa with pyloric atresia. Nat Genet 10: 229–234, 1995

    Article  PubMed  CAS  Google Scholar 

  9. Fornaro M, Tallini G, Zheng DQ, Flanagan WM, Manzotti M, Languino LR: p27kip1 acts as a downstream effector of and is coexpressed with the β1C integrin in prostatic adenocarcinoma. J Clin Invest 103: 321–329, 1999

    Article  PubMed  CAS  Google Scholar 

  10. Patriarca C, Alfano RM, Sonnenberg A, Graziani D, Cassani B, de Melker A, Colombo P, Languino LR, Fornaro M, Warren WH, Coggi G, Gould VE: Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas. Hum Pathol 29: 1208–1215, 1998

    Article  PubMed  CAS  Google Scholar 

  11. Manzotti M, Dell’Orto P, Maisonneuve P, Fornaro M, Languino LR, Viale G: Down-regulation of β1C integrin in breast carcinomas correlates with high proliferative fraction, high hislological grade, and larger size. Am J Pathol 156: 169–174, 2000

    PubMed  CAS  Google Scholar 

  12. Perlino E, Lovecchio M, Vacca RA, Fornaro M, Moro L, Ditonno P, Battaglia M, Selvaggi FP, Mastropasqua MG, Bufo P, Languino LR: Regulation of mRNA and protein levels of β1 integrin variants in human prostate carcinoma. Am J Pathol 157: 1727–1734, 2000

    PubMed  CAS  Google Scholar 

  13. Belkin AM, Retta SF, Pletjushkina OY, Balzac F, Silengo L, Fassler R, Koteliansky VE, Burridge K, Tarone G: Muscle β1D integrin reinforces the cytoskeleton-matrix link: Modulation of integrin adhesive function by alternative splicing. J Cell Biol 139:1583–1595, 1997

    Article  PubMed  CAS  Google Scholar 

  14. Retta SF, Balzac F, Ferraris P, Belkin AM, Fassler R, Humphries MJ, De Leo G, Silengo L, Tarone G: β1-integrin cytoplasmic subdomains involved in dominant negative function. Mol Biol Cell 9: 715–731, 1998

    PubMed  CAS  Google Scholar 

  15. Fornaro M, Steger CA, Bennett AM, Wu JJ, Languino LR: Differential role of β1C and β1A integrin cytoplasmic variants in modulating focal adhesion kinase, protein kinase B/AKT, and Ras/Mitogen-activated protein kinase pathways. Mol Biol Cell 11: 2235–2249, 2000

    PubMed  CAS  Google Scholar 

  16. Bottazzi ME, Assoian RK: The extracellular matrix and mitogenic growth factors control G1 phase cyclins and cyclin-dependent kinase inhibitors. Trends Cell Biol 7: 348–352, 1997

    Article  CAS  PubMed  Google Scholar 

  17. Frisch SM, Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol 9: 701–706, 1997

    Article  PubMed  CAS  Google Scholar 

  18. Schwartz MA, Schaller MD, Ginsberg MH: Integrins: Emerging paradigms of signal transduction. Annu Rev Cell DevBio 11:549–599, 1995

    Article  CAS  Google Scholar 

  19. Holly SP, Larson MK, Parise LV: Multiple roles of integrins in cell motility. Exp Cell Res 261: 69–74, 2000

    Article  PubMed  CAS  Google Scholar 

  20. Parise LV, Lee J, Juliano RL: New aspects of integrin signaling in cancer. Semin Cancer Biol 10: 407–414, 2000

    Article  PubMed  CAS  Google Scholar 

  21. Ruoslahti E, Reed JC: Anchorage dependence, integrins and apoptosis. Cell 77: 477–478, 1994

    Article  PubMed  CAS  Google Scholar 

  22. Assoian RK, Schwartz MA: Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression. Curr Opin Genet Dev 11: 48–53, 2001

    Article  PubMed  CAS  Google Scholar 

  23. Henriet P, Zhong ZD, Brooks PC, Weinberg KI, DeClerck YA: Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1. Proc Natl Acad Sci USA 97: 10026–10031, 2000

    Article  PubMed  CAS  Google Scholar 

  24. Qiang YW, Kitagawa M, Higashi M, Ishii G, Morimoto C, Harigaya K: Activation of mitogen-activated protein kinase throughα5β1 integrin is required for cell cycle progression of B progenitor cell line, Reh, on human marrow stromal cells. Exp Hematol 28: 1147–1157, 2000

    Article  PubMed  CAS  Google Scholar 

  25. Tsihlias J, Kapusta LR, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, Catzavelos GC, Koltz LH, Slingerland M: Loss of cyclin-dependent kinase inhibitor p27kip1 is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res 58: 542–548, 1998

    PubMed  CAS  Google Scholar 

  26. Yang RM, Naitoh J, Murphy M, Wang HJ, Phillipson J, deKernion JB, Loda M, Reiter RE: Low P27 expression predicts poor disease-free survival in patients with prostate cancer. J Urol 159: 941–945, 1998

    Article  PubMed  CAS  Google Scholar 

  27. Catzavelos C, Bhattacharya N, Ung YC, Wilson JA, Roncari L, Sandhu C, Shaw P, Yeger H, Morava-Protzner I, Kapusta L, Franssen E, Pritchard KI, Slingerland JM: Decreased levels of the cell-cycle inhibitor p27Kip1 protein: Prognostic implications in primary breast cancer. Nat Med 3: 227–230, 1997

    Article  PubMed  CAS  Google Scholar 

  28. Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM: Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat Med 3: 222–226, 1997

    Article  PubMed  CAS  Google Scholar 

  29. Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M: Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 3: 231–234, 1997

    Article  PubMed  CAS  Google Scholar 

  30. Cheville J, Lloyd R, Sebo T, Cheng L, Erickson L, Bostwick D, Lohse C, Wollan P: Expression of p27kip1 in prostatic adenocarcinoma. Mod Pathol 11: 324–328, 1998

    PubMed  CAS  Google Scholar 

  31. Erdamar S, Yang G, Harper JW, Lu X, Kattan MW, Thompson TC, Wheeler TM: Levels of expression of p27KIP1 protein in human prostate and prostate cancer: An immunohistochemical analysis. Mod Pathol 12: 751–755, 1999

    PubMed  CAS  Google Scholar 

  32. Fernandez PL, Arce Y, Farre X, Martinez A, Nadal A, Rey MJ, Peiro N, Campo E, Cardesa A: Expression of p27/Kip1 is down-regulated in human prostate carcinoma progression. J Pathol 187: 563–566, 1999

    Article  PubMed  CAS  Google Scholar 

  33. Fornaro M, Tallini G, Bofetiado CJM, Bosari S, Languino LR: Down-regulation of β1C integrin,aninhibitor of cell proliferation, in prostate carcinoma. Am J Pathol 149: 765–773, 1996

    PubMed  CAS  Google Scholar 

  34. Fornaro M, Manzotti M, Tallini G, Slear AE, Bosari S, Ruoslahti E, Languino LR: β1C integrin in epithelial cells correlates with a nonproliferative phenotype: Forced expression of β1C inhibits prostate epithelial cell proliferation. Am J Pathol 153: 1079–1087, 1998

    PubMed  CAS  Google Scholar 

  35. Zheng DQ, Woodard AS, Fornaro M, Tallini G, Languino LR: Prostatic carcinoma cell migration via α,β3 integrin is modulated by a focal adhesion kinase pathway. Cancer Res 59: 1655–1664, 1999

    PubMed  CAS  Google Scholar 

  36. Nagle RB, Knox JD, Wolf C, Bowden GT, Cress AE: Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. J Cell Biochem (19 Suppl): 232–237, 1994

    Google Scholar 

  37. Trikha M, Cai Y, Grignon D, Honn KV: Identification of a novel truncated αIIb integrin. Cancer Res 58: 4771–4775, 1998

    PubMed  CAS  Google Scholar 

  38. Nagle RB, Hao J, Knox JD, Dalkin BL, Clark V, Cress AE: Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue. Am J Pathol 146: 1498–1507, 1995

    PubMed  CAS  Google Scholar 

  39. Allen MV, Smith GJ, Juliano R, Maygarden SJ, Mohler JL: Downregulation of the β4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia. Hum Pathol 29:311–318, 1998

    Article  PubMed  CAS  Google Scholar 

  40. Davis TL, Cress AE, Dalkin BL, Nagle RB: Unique expression pattern of the α6β4 integrin and laminin-5 in human prostate carcinoma. Prostate 46: 240–248, 2001

    Article  PubMed  CAS  Google Scholar 

  41. Bonkhoff H, Stein U, Remberger K: Differential expression of α6 and α2 very late antigen integrins in the normal, hyperplastic, and neoplastic prostate: Simultaneous demonstration of cell surface receptors and their extracellular ligands. Hum Pathol 24: 243–248, 1993

    Article  PubMed  CAS  Google Scholar 

  42. Bonkhoff H: Analytical molecular pathology of epithelialstromal interactions in the normal and neoplastic prostate. Analyt Quant Cytol Histol 20: 437–442, 1998

    CAS  Google Scholar 

  43. Murant SJ, Handley J, Stower M, Reid N, Cussenot O, Maitland NJ: Coordinated changes in expression of cell adhesion molecules in prostate cancer. Eur J Cancer 33: 263–271, 1997

    Article  PubMed  CAS  Google Scholar 

  44. Hao J, Jackson L, Calaluce R, McDaniel K, Dalkin BL, Nagle RB: Investigation into the mechanism of the loss of laminin5 (α3β3γ2) expression in prostate cancer. Am J Pathol 158: 1129–1135, 2001

    PubMed  CAS  Google Scholar 

  45. Hemler M, Mannion B, Berditchevski F: Association of TM4SF proteins with integrins: Relevance to cancer. Biochim Biophys Acta 1287: 67–71, 1996

    PubMed  Google Scholar 

  46. Augustus M, Moul JW, Srivastava S: The Molecular Phenotype of the Malignant Prostate, IOS Press, Washington DC, 1999

    Google Scholar 

  47. Burton JL, Oakley N, Anderson JB: Recent advances in the histopathology and molecular biology of prostate cancer. BJU Int 85: 87–94, 2000

    Article  PubMed  CAS  Google Scholar 

  48. Guan JL, Trevithick JE, Hynes RO: Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120 kDa protein. Cell Regul 2: 951, 1991

    PubMed  CAS  Google Scholar 

  49. Kornberg L, Earp H, Turner C, Prockop C, Juliano R: Signal transduction by integrins: Increased protein tyrosine phosphorylation caused by clustering in β1 integrins. Proc Natl Acad Sci USA 88: 8392–8396, 1991

    Article  PubMed  CAS  Google Scholar 

  50. Schaller MD: Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 1540: 1–21, 2001

    Article  PubMed  CAS  Google Scholar 

  51. Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T, Alzawa S: Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377: 539–543, 1995

    Article  PubMed  CAS  Google Scholar 

  52. Ilic D, Kanazawa S, Furuta Y, Yamamoto T, Aizawa S: Impairment of mobility in endodermal cells by FAK deficiency. Exp Cell Res 222: 298–303, 1996

    Article  PubMed  CAS  Google Scholar 

  53. Gary LA, Chang JF, Guan J-L: Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn J Cell Sci 109: 1787–1794, 1996

    Google Scholar 

  54. Gilmore A, Romer H: Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation. Mol Biol Cell 7: 1209–1224, 1996

    PubMed  CAS  Google Scholar 

  55. Tremblay L, Hauck W, Aprikian AG, Begin LR, Chapdelaine A, Chevalier S: Focaladhesionkinase pp125FAK expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma. Int J Cancer 68: 164–171, 1996

    Article  PubMed  CAS  Google Scholar 

  56. Stanzione R, Picascia A, Chieffi P, Imbimbo C, Palmieri A, Mirone V, Staibano S, Franco R, De Rosa G, Schlessinger J, Tramontano D: Variations of proline-rich kinase Pyk2 expression correlate with prostate cancer progression. Lab Invest 81: 51–59, 2001

    PubMed  CAS  Google Scholar 

  57. Sieg DJ, Hauck CR, Schlaepfer DD: Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J Cell Sci 112: 2677–2691, 1999

    PubMed  CAS  Google Scholar 

  58. Klinghoffer RA, Sachsenmaier C, Cooper JA, Soriano P: Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J 18: 2459–2471, 1999

    Article  PubMed  CAS  Google Scholar 

  59. Slack JK, Adams RB, Rovin JD, Bissonette EA, Stoker CE, Parsons JT: Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene 20:1152–1163, 2001

    Article  PubMed  CAS  Google Scholar 

  60. Keely P, Parise L, Juliano R: Integrins and GTPases in tumor cell growth, motility and invasion. Trends Cell Biol 8: 101–106, 1998

    Article  PubMed  CAS  Google Scholar 

  61. Rameh LE, Cantley LC: The role of phosphoinositide 3-kinase lipid products in cell function. J Biol Chem 274: 8347–8350, 1999

    Article  PubMed  CAS  Google Scholar 

  62. Jiang BH, Aoki M, Zheng JZ, Li J, Vogt PK: Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B. Proc Natl Acad Sci USA 96: 2077–2081, 1999

    Article  PubMed  CAS  Google Scholar 

  63. Morales-Ruiz M, Fulton D, Sowa G, Languino LR, Fujio Y, Walsh K, Sessa WC: Vascular endothelial growth factor-stimulated actin reorganization and migration of endothelial cells is regulated via the serine/threonine kinase Akt. Circ Res 86: 892–896, 2000

    PubMed  CAS  Google Scholar 

  64. Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J: Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J 16: 2783–2793, 1997

    Article  PubMed  CAS  Google Scholar 

  65. King WG, Mattaliano MD, Chan TO, Tsichlis PN, Brugge JS: Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation. Mol Cell Biol 17: 4406–4418, 1997

    PubMed  CAS  Google Scholar 

  66. Chen H-C, Guan J-L: Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase, Proc Natl Acad Sci USA 91: 10148–10152, 1994

    Article  PubMed  CAS  Google Scholar 

  67. Downward J: Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10: 262–267, 1998

    Article  PubMed  CAS  Google Scholar 

  68. Sun M, Wang G, Paciga JE, Feldman RI, Yuan ZQ, Ma XL, Shelley SA, Jove R, Tsichlis PN, Nicosia SV, Cheng JQ: AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am J Pathol 159: 431–437, 2001

    PubMed  CAS  Google Scholar 

  69. Paweletz CP, Charboneau L, Bichsel VE, Simone NL, Chen T, Gillespie JW, Emmert-Buck MR, Roth MJ, Petricoin IE, Liotta LA: Reverse phase protein microarrays which capture disease progression show activation of prosurvival pathways at the cancer invasion front. Oncogene 20: 1981–1989, 2001

    Article  PubMed  CAS  Google Scholar 

  70. Mercurio AM, Rabinovitz I, Shaw LM: The α6β4 integrin and epithelial cell migration. Curr Opin Cell Biol 13: 541–545, 2001

    Article  PubMed  CAS  Google Scholar 

  71. Maehama T, Dixon JE: PTEN: A tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol 9: 125–128, 1999

    Article  PubMed  CAS  Google Scholar 

  72. Tamura M, Gu J, Tran H, Yamada KM: PTEN gene and integrin signaling in cancer. J Natl Cancer Inst 91: 1820–1828, 1999

    Article  PubMed  CAS  Google Scholar 

  73. Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading and focal adhesions by tumor suppressor PTEN. Science 280: 1614–1617, 1998

    Article  PubMed  CAS  Google Scholar 

  74. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947, 1997

    Article  PubMed  CAS  Google Scholar 

  75. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV: Identification of acandidate tumour suppressor gene, MMAC1, at chromosome 1023.3 that is mutated in multiple advanced cancers. Nat Genet 15:356–362, 1997

    Article  PubMed  CAS  Google Scholar 

  76. Cairns P, Okami K, Halachmi S, Halachmi N, Esteller M, Herman JG, Jen J, Isaacs WB, Bova GS, Sidransky D: Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57: 4997–5000, 1997

    PubMed  CAS  Google Scholar 

  77. Suzuki H, Freije D, Nusskern DR, Okami K, Cairns P, Sidransky D, Isaacs WB, Bova GS: Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res 58: 204–209, 1998

    PubMed  CAS  Google Scholar 

  78. Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen KL, Vinson VL, Gumpper KL, Ellis L, El-Naggar A, Frazier M, Jasser S. Langford LA, Lee J, Mills GB, Pershouse MA, Pollack RE, Tornos C, Troncoso P, Yung WK, Fujii G, Berson A, Steck PA, et al.: MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 57: 5221–5225, 1997

    PubMed  CAS  Google Scholar 

  79. Vlietstra RJ, van Alewijk DCJG, Hermans KGL, van Steenbrugge GJ, Trapman J: Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. Cancer Res 58: 2720–2723, 1998

    PubMed  CAS  Google Scholar 

  80. McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR; Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 59: 4291–4296, 1999

    PubMed  CAS  Google Scholar 

  81. Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ: Increasing complexity of Ras signaling. Oncogene 17: 1395–1413, 1998

    Article  PubMed  CAS  Google Scholar 

  82. Robinson MJ, Cobb MH: Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9: 180–186, 1997

    Article  PubMed  CAS  Google Scholar 

  83. Chang L, Karin M: Mammalian MAP kinase signalling cascades. Nature 410: 37–40, 2001

    Article  PubMed  CAS  Google Scholar 

  84. Clark E, Hynes R: Ras activation is necesary for integrin-mediated activation of extracellular signal-regulated kinase 2 and cytosolic phospholipase A2 but not for cytoskeletal organization. J Biol Chem 271:14814–14818, 1996

    Article  PubMed  CAS  Google Scholar 

  85. Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE, Giancotti FG: The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87: 733–743, 1996

    Article  PubMed  CAS  Google Scholar 

  86. Mainiero F, Murgia C, Wary KK, Curatola AM, Pepe A, Blumemberg M, Westwick JK, Der CJ, Giancotti FG: The coupling of α6β4 integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation. EMBO J 16: 2365–2375, 1997

    Article  PubMed  CAS  Google Scholar 

  87. Miranti CK, Ohno S, Brugge JS: Protein kinase C regulated integrin-induced activation of the extracellular regulated kinase pathway upstream of Shc. J Biol Chem 274: 10571–10581, 1999

    Article  PubMed  CAS  Google Scholar 

  88. Schlaepfer DD, Hunter T: Integrin signalling and tyrosine phosphorylation: Just the FAKs? Trends Cell Biol 8: 151–157, 1998

    Article  PubMed  CAS  Google Scholar 

  89. Howe A, Aplin AE, Alahari SK, Juliano RL: Integrin signaling and cell growth control. Curr Opin Cell Biol 10: 220–231, 1998

    Article  PubMed  CAS  Google Scholar 

  90. Schwartz MA, Assoian RK: Integrins and cell proliferation: Regulation of cyclin-dependentkinases viacytoplasmic signaling pathways. J Cell Sci 114: 2553–2560, 2001

    PubMed  CAS  Google Scholar 

  91. Sastry SK, Lakonishok M, Wu S, Truong TQ, Huttenlocher A, Turner CE, Horwitz AF: Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal. J Cell Biol 144: 1295–1309, 1999

    Article  PubMed  CAS  Google Scholar 

  92. Gu J, Tamura M, Pankov R, Danen EH, Takino T, Matsumoto K, Yamada KM: Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J Cell Biol 146: 389–403, 1999

    Article  PubMed  CAS  Google Scholar 

  93. Cheresh DA, Leng J, Klemke RL: Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells. J Cell Biol 146: 1107–1116, 1999

    Article  PubMed  CAS  Google Scholar 

  94. Frisch SM, Screaton RA: Anoikis mechanisms. Curr Opin Cell Biol 13: 555–562, 2001

    Article  PubMed  CAS  Google Scholar 

  95. Le Gall M, Chambard JC, Breittmayer JP, Grall D, Pouyssegur J, Van Obberghen-Schilling E: The p42/p44 MAP kinase pathway prevents apoptosis induced by anchorage and serum removal. Mol Biol Cell 11: 1103–1112, 2000

    PubMed  Google Scholar 

  96. Rosen K, Rak J, Leung T, Dean NM, Kerbel RS, Filmus J: Activated Ras prevents downregulation of Bcl-X(L) triggered by detachment from the extracellular matrix. A mechanism of Ras-induced resistance to anoikis in intestinal epithelial cells. J Cell Biol 149:447–456, 2000

    Article  PubMed  CAS  Google Scholar 

  97. Cho SY, Klemke RL: Extracellular-regulated kinase activation and CAS/Crk coupling regulate cell migration and suppress apoptosis during invasion of the extracellular matrix. J Cell Biol 149: 223–236, 2000

    Article  PubMed  CAS  Google Scholar 

  98. Gioeli D, Mandell JW, Petroni GR, Frierson HF Jr, Weber MJ: Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 59:279–284, 1999

    PubMed  CAS  Google Scholar 

  99. Magi-Galluzzi C, Mishra R, Fiorentino M, Montironi R, Yao H, Capodieci P, Wishnow K, Kaplan I, Stork PJ, Loda M: Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. Lab Invest 76: 37–51, 1997

    PubMed  CAS  Google Scholar 

  100. Price DT, Rocca GD, Quo C, Ballo MS, Schwinn DA, Luttrell LM: Activation of extracellular signal-regulated kinase in human prostate cancer. J Urol 162: 1537–1542, 1999

    Article  PubMed  CAS  Google Scholar 

  101. Vaux DL, Cory S, Adams JM: Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335: 440–442, 1988

    Article  PubMed  CAS  Google Scholar 

  102. Reed JC: Mechanisms of apoptosis. Am J Pathol 157:1415–1430, 2000

    PubMed  CAS  Google Scholar 

  103. Zhang Z, Vuori K, Reed JC, Ruoslahti E: The α5β1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression. Proc Natl Acad Sci USA 92:6161–6165, 1995

    Article  PubMed  CAS  Google Scholar 

  104. Matter ML, Ruoslahti E: A signaling pathway from the α5β1 and αVβ3 integrins that elevates bcl-2 transcription. J Biol Chem 276: 27757–27763, 2001

    Article  PubMed  CAS  Google Scholar 

  105. Bruckheimer EM, Gjertsen BT, McDonnell TJ: Implications of cell death regulation in the pathogenesis and treatment of prostate cancer. Semin Oncol 26: 382–398, 1999

    PubMed  CAS  Google Scholar 

  106. Colombel M, Symmans F, Gil S, O’Toole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S, Buttyan R: Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143: 390–400, 1993

    PubMed  CAS  Google Scholar 

  107. Del Bufalo D, Biroccio A, Leonetti C, Zupi G: Bcl-2 overexpression enhances the metastatic potential of a human breast cancer line. FASEB J 11: 947–953, 1997

    PubMed  Google Scholar 

  108. Knox JD, Cress AE, Clark V, Manriquez L, Affinito KitSahn, Dalkin BL, Nagle RB: Differential expression of extracellular matrix molecules and the α6-integrins in the normal and neoplastic prostate. Am J Pathol 145: 167–174, 1994

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Yale University School of Medicine, P.O. Box 208023, 310 Cedar Street, New Haven, CT, 06520, USA

    Mara Fornaro, Thomas Manes & Lucia R. Languino

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  1. Mara Fornaro
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  2. Thomas Manes
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  1. The Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Michael L. Cher

  2. Wayne State University School of Medicine, Detroit, MI, USA

    Avraham Raz  & Kenneth V. Honn  & 

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© 2002 Kluwer Academic Publishers

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Fornaro, M., Manes, T., Languino, L.R. (2002). Integrins and prostate cancer metastases. In: Cher, M.L., Raz, A., Honn, K.V. (eds) Prostate Cancer: New Horizons in Research and Treatment. Developments in Oncology, vol 81. Springer, Boston, MA. https://doi.org/10.1007/0-306-48143-X_12

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  • DOI: https://doi.org/10.1007/0-306-48143-X_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7352-6

  • Online ISBN: 978-0-306-48143-7

  • eBook Packages: Springer Book Archive

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