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Caveolins in Cancer Pathogenesis, Prevention and Therapy pp 91–104Cite as

Caveolin-1 and Breast Cancer

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Part of the book series: Current Cancer Research ((CUCR))

Abstract

Caveolin-1 (Cav-1), the main protein component of caveolae, is expressed in several differentiated cell types such as mammary epithelial cells. It is well-established that caveolae function as an organizing center that recruits and sequesters various signaling molecules. Several studies have now clearly demonstrated a role for Cav-1 in the development of breast cancer. Indeed, genetic ablation of Cav-1 in mice causes mammary epithelial hyperplasia. Importantly, a dominant-negative mutant of Cav-1 (P132L) has been observed in 19% of breast cancer patients with estrogen receptor-positive tumors. Furthermore, it has been demonstrated that a loss of stromal Cav-1 in breast cancer-associated fibroblasts (CAFs) is a crucial predictor of tumor recurrence, metastases formation, tamoxifen-resistance, and poor clinical outcome in these patients. Moreover, a new theory termed “autophagic tumor stroma model of cancer” has been proposed regarding tumor progression. In this theory, a lack of Cav-1 in CAFs drives hypoxia, oxidative stress, and autophagy/mitophagy in the breast cancer micro-environment. Finally, these promising findings could provide new potential therapeutic targets that could contribute to the development of more effective therapies and patient stratification.

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References

  1. Lisanti MP, Scherer P, Tang Z-L, Sargiacomo M (1994) Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol 4:231–235

    Article  PubMed  CAS  Google Scholar 

  2. Okamoto T, Schlegel A, Scherer PE, Lisanti MP (1998) Caveolins, a family of scaffolding proteins for organizing “pre-assembled signaling complexes” at the plasma membrane. J Biol Chem 273:5419–5422

    Article  PubMed  CAS  Google Scholar 

  3. Anderson RGW (1998) The caveolae membrane system. Annu Rev Biochem 67:199–225

    Article  PubMed  CAS  Google Scholar 

  4. Brown DA, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14:111–136

    Article  PubMed  CAS  Google Scholar 

  5. Galbiati F, Razani B, Lisanti MP (2001) Emerging themes in lipid rafts and caveolae. Cell 106:403–411

    Article  PubMed  CAS  Google Scholar 

  6. Williams TM, Lisanti MP (2004) The Caveolin genes: from cell biology to medicine. Ann Med 36:584–595

    Article  PubMed  CAS  Google Scholar 

  7. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–467

    Article  PubMed  CAS  Google Scholar 

  8. Mercier I, Jasmin JF, Pavlides S, Minetti C, Flomenberg N, Pestell RG, Frank PG, Sotgia F, Lisanti MP (2009) Clinical and translational implications of the caveolin gene family: lessons from mouse models and human genetic disorders. Lab Invest 89:614–623

    Article  PubMed  CAS  Google Scholar 

  9. Engelman JA, Zhang XL, Lisanti MP (1998) Genes encoding human caveolin-1 and -2 are co-localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers. FEBS Lett 436:403–410

    Article  PubMed  CAS  Google Scholar 

  10. Glenney JR (1989) Tyrosine phosphorylation of a 22 kD protein is correlated with transformation with Rous sarcoma virus. J Biol Chem 264:20163–20166

    PubMed  CAS  Google Scholar 

  11. Koleske AJ, Baltimore D, Lisanti MP (1995) Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci USA 92:1381–1385

    Article  PubMed  CAS  Google Scholar 

  12. Razani B, Altschuler Y, Zhu L, Pestell RG, Mostov KE, Lisanti MP (2000) Caveolin-1 expression is down-regulated in cells transformed by the human papilloma virus in a p53-dependent manner. Replacement of caveolin-1 expression suppresses HPV-mediated cell transformation. Biochemistry 39:13916–13924

    Article  PubMed  CAS  Google Scholar 

  13. Engelman JA, Lee RJ, Karnezis A, Bearss DJ, Webster M, Siegel P, Muller WJ, Windle JJ, Pestell RG, Lisanti MP (1998) Reciprocal regulation of Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for mammary tumorigenesis. J Biol Chem 273:20448–20455

    Article  PubMed  CAS  Google Scholar 

  14. Volonte D, Galbiati F, Pestell RG, Lisanti MP (2001) Cellular stress induces the tyrosine phosphorylation of caveolin-1 (Tyr(14)) via activation of p38 mitogen-activated protein kinase and c-Src kinase. Evidence for caveolae, the actin cytoskeleton, and focal adhesions as mechanical sensors of osmotic stress. J Biol Chem 276:8094–8103

    Article  PubMed  CAS  Google Scholar 

  15. Zhang W, Razani B, Altschuler Y, Bouzahzah B, Mostov KE, Pestell RG, Lisanti MP (2000) Caveolin-1 inhibits epidermal growth factor-stimulated lamellipod extension and cell migration in metastatic mammary adenocarcinoma cells (MTLn3). Transformation suppressor effects of adenovirus-mediated gene delivery of caveolin-1. J Biol Chem 275:20717–20725

    Article  PubMed  CAS  Google Scholar 

  16. Stupack DG, Cheresh DA (2002) Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci 115:3729–3738

    Article  PubMed  CAS  Google Scholar 

  17. Witkiewicz AK, Dasgupta A, Sammons S, Er O, Potoczek MB, Guiles F, Sotgia F, Brody JR, Mitchell EP, Lisanti MP (2010) Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers. Cancer Biol Ther 10:135–143

    Article  PubMed  Google Scholar 

  18. Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou HJ, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138

    Article  PubMed  CAS  Google Scholar 

  19. Schubert W, Frank PG, Woodman SE, Hyogo H, Cohen DE, Chow CW, Lisanti MP (2002) Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 277:40091–40098

    Article  PubMed  CAS  Google Scholar 

  20. Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293:2449–2452

    Article  PubMed  CAS  Google Scholar 

  21. Lee H, Park DS, Razani B, Russell RG, Pestell RG, Lisanti MP (2002) Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia. Am J Pathol 161:1357–1369

    Article  PubMed  CAS  Google Scholar 

  22. Sotgia F, Rui H, Bonuccelli G, Mercier I, Pestell RG, Lisanti MP (2006) Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers. Cancer Res 66:10647–10651

    Article  PubMed  CAS  Google Scholar 

  23. Liu P, Ying Y, Anderson RG (1997) Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae. Proc Natl Acad Sci USA 94:13666–13670

    Article  PubMed  CAS  Google Scholar 

  24. Smart EJ, Ying YS, Mineo C, Anderson RG (1995) A detergent-free method for purifying caveolae membrane from tissue culture cells. Proc Natl Acad Sci USA 92:10104–10108

    Article  PubMed  CAS  Google Scholar 

  25. Engelman JA, Chu C, Lin A, Jo H, Ikezu T, Okamoto T, Kohtz DS, Lisanti MP (1998) Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo. A role for the caveolin-scaffolding domain. FEBS Lett 428:205–211

    Article  PubMed  CAS  Google Scholar 

  26. Galbiati F, Volonte D, Engelman JA, Watanabe G, Burk R, Pestell RG, Lisanti MP (1998) Targeted down-regulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade. EMBO J 17:6633–6648

    Article  PubMed  CAS  Google Scholar 

  27. Engelman JA, Zhang XL, Razani B, Pestell RG, Lisanti MP (1999) p42/44 MAP kinase-dependent and -independent signaling pathways regulate caveolin-1 gene expression. Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter activity. J Biol Chem 274:32333–32341

    Article  PubMed  CAS  Google Scholar 

  28. Capozza F, Williams TM, Schubert W, McClain S, Bouzahzah B, Sotgia F, Lisanti MP (2003) Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermal hyperplasia and tumor formation. Am J Pathol 162:2029–2039

    Article  PubMed  CAS  Google Scholar 

  29. Cohen AW, Razani B, Wang XB, Combs TP, Williams TM, Scherer PE, Lisanti MP (2003) Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol Cell Physiol 285:C222–C235

    PubMed  CAS  Google Scholar 

  30. Williams TM, Lee H, Cheung MW, Cohen AW, Razani B, Iyengar P, Scherer PE, Pestell RG, Lisanti MP (2004) Combined loss of INK4a and caveolin-1 synergistically enhances cell proliferation and oncogene-induced tumorigenesis: role of INK4a/CAV-1 in mammary epithelial cell hyperplasia. J Biol Chem 279:24745–24756

    Article  PubMed  CAS  Google Scholar 

  31. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A (1991) A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 350:512–515

    Article  PubMed  CAS  Google Scholar 

  32. Lew DJ, Dulic V, Reed SI (1991) Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell 66:1197–1206

    Article  PubMed  CAS  Google Scholar 

  33. Lammie GA, Fantl V, Smith R, Schuuring E, Brookes S, Michalides R, Dickson C, Arnold A, Peters G (1991) D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. Oncogene 6:439–444

    PubMed  CAS  Google Scholar 

  34. Bartkova J, Lukas J, Muller H, Lutzhoft D, Strauss M, Bartek J (1994) Cyclin D1 protein expression and function in human breast cancer. Int J Cancer 57:353–361

    Article  PubMed  CAS  Google Scholar 

  35. Gillett C, Fantl V, Smith R, Fisher C, Bartek J, Dickson C, Barnes D, Peters G (1994) Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 54:1812–1817

    PubMed  CAS  Google Scholar 

  36. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677

    Article  PubMed  CAS  Google Scholar 

  37. Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ (1993) Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev 7:331–342

    Article  PubMed  CAS  Google Scholar 

  38. Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18:753–761

    PubMed  CAS  Google Scholar 

  39. Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA (1995) Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82:621–630

    Article  PubMed  CAS  Google Scholar 

  40. Pestell RG, Albanese C, Reutens AT, Segall JE, Lee RJ, Arnold A (1999) The cyclins and cyclin-dependent kinase inhibitors in hormonal regulation of proliferation and differentiation. Endocr Rev 20:501–534

    Article  PubMed  CAS  Google Scholar 

  41. Liu JJ, Chao JR, Jiang MC, Ng SY, Yen JJ, Yang-Yen HF (1995) Ras transformation results in an elevated level of cyclin D1 and acceleration of G1 progression in NIH 3T3 cells. Mol Cell Biol 15:3654–3663

    PubMed  CAS  Google Scholar 

  42. Lee RJ, Albanese C, Fu M, D’Amico M, Lin B, Watanabe G, Haines GK 3rd, Siegel PM, Hung MC, Yarden Y, Horowitz JM, Muller WJ, Pestell RG (2000) Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway. Mol Cell Biol 20:672–683

    Article  PubMed  CAS  Google Scholar 

  43. Hulit J, Bash T, Fu M, Galbiati F, Albanese C, Sage DR, Schlegel A, Zhurinsky J, Shtutman M, Ben-Ze’ev A, Lisanti MP, Pestell RG (2000) The cyclin D1 gene is transcriptionally repressed by caveolin-1. J Biol Chem 275:21203–21209

    Article  PubMed  CAS  Google Scholar 

  44. Williams TM, Medina F, Badano I, Hazan RB, Hutchinson J, Muller WJ, Chopra NG, Scherer PE, Pestell RG, Lisanti MP (2004) Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J Biol Chem 279:51630–51646

    Article  PubMed  CAS  Google Scholar 

  45. Williams TM, Sotgia F, Lee H, Hassan G, Di Vizio D, Bonuccelli G, Capozza F, Mercier I, Rui H, Pestell RG, Lisanti MP (2006) Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Am J Pathol 169:1784–1801

    Article  PubMed  CAS  Google Scholar 

  46. Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, Hayakawa T, Hamaguchi M (2001) Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res 61:2361–2364

    PubMed  CAS  Google Scholar 

  47. Li L, Ren CH, Tahir SA, Ren C, Thompson TC (2003) Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol Cell Biol 23:9389–9404

    Article  PubMed  CAS  Google Scholar 

  48. Li T, Sotgia F, Vuolo MA, Li M, Yang WC, Pestell RG, Sparano JA, Lisanti MP (2006) Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor alpha-positive status. Am J Pathol 168:1998–2013

    Article  PubMed  CAS  Google Scholar 

  49. Mercier I, Casimiro MC, Zhou J, Wang C, Plymire C, Bryant KG, Daumer KM, Sotgia F, Bonuccelli G, Witkiewicz AK, Lin J, Tran TH, Milliman J, Frank PG, Jasmin JF, Rui H, Pestell RG, Lisanti MP (2009) Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of DCIS-like mammary lesions. Am J Pathol 174:1172–1190

    Article  PubMed  CAS  Google Scholar 

  50. Borowsky AD, Namba R, Young LJ, Hunter KW, Hodgson JG, Tepper CG, McGoldrick ET, Muller WJ, Cardiff RD, Gregg JP (2005) Syngeneic mouse mammary carcinoma cell lines: two closely related cell lines with divergent metastatic behavior. Clin Exp Metastasis 22:47–59

    Article  PubMed  CAS  Google Scholar 

  51. Namba R, Young LJ, Abbey CK, Kim L, Damonte P, Borowsky AD, Qi J, Tepper CG, MacLeod CL, Cardiff RD, Gregg JP (2006) Rapamycin inhibits growth of premalignant and malignant mammary lesions in a mouse model of ductal carcinoma in situ. Clin Cancer Res 12:2613–2621

    Article  PubMed  CAS  Google Scholar 

  52. Bonuccelli G, Casimiro MC, Sotgia F, Wang C, Liu M, Katiyar S, Zhou J, Dew E, Capozza F, Daumer KM, Minetti C, Milliman JN, Alpy F, Rio MC, Tomasetto C, Mercier I, Flomenberg N, Frank PG, Pestell RG, Lisanti MP (2009) Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature. Am J Pathol 174:1650–1662

    Article  PubMed  CAS  Google Scholar 

  53. Hennighausen L, Robinson GW (1998) Think globally, act locally: the making of a mouse mammary gland. Genes Dev 12:449–455

    Article  PubMed  CAS  Google Scholar 

  54. Freeman ME, Kanyicska B, Lerant A, Nagy G (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80:1523–1631

    PubMed  CAS  Google Scholar 

  55. Park DS, Lee H, Riedel C, Hulit J, Scherer PE, Pestell RG, Lisanti MP (2001) Prolactin negatively regulates caveolin-1 gene expression in the mammary gland during lactation, via a Ras-dependent mechanism. J Biol Chem 276:48389–48397

    PubMed  CAS  Google Scholar 

  56. Park DS, Lee H, Frank PG, Razani B, Nguyen AV, Parlow AF, Russell RG, Hulit J, Pestell RG, Lisanti MP (2002) Caveolin-1-deficient mice show accelerated mammary gland development during pregnancy, premature lactation, and hyperactivation of the Jak-2/STAT5a signaling cascade. Mol Biol Cell 13:3416–3430

    Article  PubMed  CAS  Google Scholar 

  57. Lindeman GJ, Wittlin S, Lada H, Naylor MJ, Santamaria M, Zhang JG, Starr R, Hilton DJ, Alexander WS, Ormandy CJ, Visvader J (2001) SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice. Genes Dev 15:1631–1636

    Article  PubMed  CAS  Google Scholar 

  58. Mercier I, Casimiro MC, Wang C, Rosenberg AL, Quong J, Minkeu A, Allen KG, Danilo C, Sotgia F, Bonuccelli G, Jasmin JF, Xu H, Bosco E, Aronow B, Witkiewicz A, Pestell RG, Knudsen ES, Lisanti MP (2008) Human breast cancer-associated fibroblasts (CAFs) show caveolin-1 downregulation and RB tumor suppressor functional inactivation: implications for the response to hormonal therapy. Cancer Biol Ther 7:1212–1225

    Article  PubMed  CAS  Google Scholar 

  59. Sotgia F, Del Galdo F, Casimiro MC, Bonuccelli G, Mercier I, Whitaker-Menezes D, Daumer KM, Zhou J, Wang C, Katiyar S, Xu H, Bosco E, Quong AA, Aronow B, Witkiewicz AK, Minetti C, Frank PG, Jimenez SA, Knudsen ES, Pestell RG, Lisanti MP (2009) Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts. Am J Pathol 174:746–761

    Article  PubMed  CAS  Google Scholar 

  60. Brotherick I, Robson CN, Browell DA, Shenfine J, White MD, Cunliffe WJ, Shenton BK, Egan M, Webb LA, Lunt LG, Young JR, Higgs MJ (1998) Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression. Cytometry 32:301–308

    Article  PubMed  CAS  Google Scholar 

  61. Ronnstrand L, Heldin CH (2001) Mechanisms of platelet-derived growth factor-induced chemotaxis. Int J Cancer 91:757–762

    Article  PubMed  CAS  Google Scholar 

  62. Machesky LM (2008) Lamellipodia and filopodia in metastasis and invasion. FEBS Lett 582:2102–2111

    Article  PubMed  CAS  Google Scholar 

  63. Sloan EK, Stanley KL, Anderson RL (2004) Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene 23:7893–7897

    Article  PubMed  CAS  Google Scholar 

  64. Guy CT, Cardiff RD, Muller WJ (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 12:954–961

    PubMed  CAS  Google Scholar 

  65. Coussens LM, Werb Z (1996) Matrix metalloproteinases and the development of cancer. Chem Biol 3:895–904

    Article  PubMed  CAS  Google Scholar 

  66. Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S (1998) Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 58:1048–1051

    PubMed  CAS  Google Scholar 

  67. Itoh T, Tanioka M, Matsuda H, Nishimoto H, Yoshioka T, Suzuki R, Uehira M (1999) Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Metastasis 17:177–181

    Article  PubMed  CAS  Google Scholar 

  68. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174

    Article  PubMed  CAS  Google Scholar 

  69. Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem 270:5331–5338

    Article  PubMed  CAS  Google Scholar 

  70. Puyraimond A, Fridman R, Lemesle M, Arbeille B, Menashi S (2001) MMP-2 colocalizes with caveolae on the surface of endothelial cells. Exp Cell Res 262:28–36

    Article  PubMed  CAS  Google Scholar 

  71. Annabi B, Lachambre M, Bousquet-Gagnon N, Page M, Gingras D, Beliveau R (2001) Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains. Biochem J 353:547–553

    Article  PubMed  CAS  Google Scholar 

  72. Galvez BG, Matias-Roman S, Yanez-Mo M, Vicente-Manzanares M, Sanchez-Madrid F, Arroyo AG (2004) Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells. Mol Biol Cell 15:678–687

    Article  PubMed  CAS  Google Scholar 

  73. Engelman JA, Wycoff CC, Yasuhara S, Song KS, Okamoto T, Lisanti MP (1997) Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates anchorage-independent growth. J Biol Chem 272:16374–16381

    Article  PubMed  CAS  Google Scholar 

  74. Zundel W, Swiersz LM, Giaccia A (2000) Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide. Mol Cell Biol 20:1507–1514

    Article  PubMed  CAS  Google Scholar 

  75. Liu J, Lee P, Galbiati F, Kitsis RN, Lisanti MP (2001) Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. Am J Physiol Cell Physiol 280:C823–C835

    PubMed  CAS  Google Scholar 

  76. Li L, Yang G, Ebara S, Satoh T, Nasu Y, Timme TL, Ren C, Wang J, Tahir SA, Thompson TC (2001) Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells. Cancer Res 61:4386–4392

    PubMed  CAS  Google Scholar 

  77. Nasu Y, Timme TL, Yang G, Bangma CH, Li L, Ren C, Park SH, DeLeon M, Wang J, Thompson TC (1998) Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells. Nat Med 4:1062–1064

    Article  PubMed  CAS  Google Scholar 

  78. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (2009) The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 8:3984–4001

    Article  PubMed  CAS  Google Scholar 

  79. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Knudsen ES, Sotgia F, Lisanti MP (2010) Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: a new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle 9:3256–3276

    Article  PubMed  CAS  Google Scholar 

  80. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F (2010) Autophagy in cancer associated fibroblasts promotes tumor cell survival: role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cell Cycle 9:3515–3533

    Article  PubMed  CAS  Google Scholar 

  81. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (2010) Ketones and lactate “fuel” tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 9:3506–3514

    Article  PubMed  CAS  Google Scholar 

  82. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, Martinez-Outschoorn UE, Howell A, Sotgia F, Lisanti MP (2010) The autophagic tumor stroma model of cancer: role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 9:3485–3505

    Article  PubMed  CAS  Google Scholar 

  83. Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, Kleer CG, Brody JR, Lisanti MP (2009) An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol 174:2023–2034

    Article  PubMed  CAS  Google Scholar 

  84. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (2010) Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the “reverse Warburg effect”: a transcriptional informatics analysis with validation. Cell Cycle 9:2201–2219

    Article  PubMed  CAS  Google Scholar 

  85. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A, Sotgia F (2010) Understanding the “lethal” drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther 10:537–542

    Article  PubMed  CAS  Google Scholar 

  86. Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, Tanowitz HB, Casimiro MC, Wang C, Pestell RG, Grieshaber P, Caro J, Sotgia F, Lisanti MP (2010) HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: autophagy drives compartment-specific oncogenesis. Cell Cycle 9:3534–3551

    Article  PubMed  CAS  Google Scholar 

  87. Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, Nakamura M, Kakudo K (2006) Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 12:1201–1207

    Article  PubMed  CAS  Google Scholar 

  88. Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, Jasmin JF, Frank PG, Pestell RG, Kleer CG, Sotgia F, Lisanti MP (2009) Towards a new “stromal-based” classification system for human breast cancer prognosis and therapy. Cell Cycle 8:1654–1658

    Article  PubMed  CAS  Google Scholar 

  89. Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, Pestell RG, Sotgia F, Rui H, Lisanti MP (2009) Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther 8:1071–1079

    Article  PubMed  CAS  Google Scholar 

  90. Di Vizio D, Morello M, Sotgia F, Pestell RG, Freeman MR, Lisanti MP (2009) An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation. Cell Cycle 8:2420–2424

    Article  PubMed  Google Scholar 

  91. Migneco G, Whitaker-Menezes D, Chiavarina B, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, Flomenberg N, Tsirigos A, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (2010) Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling. Cell Cycle 9:2412–2422

    Article  PubMed  CAS  Google Scholar 

  92. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3:347–361

    Article  PubMed  Google Scholar 

  93. Steeg PS (2003) Angiogenesis inhibitors: motivators of metastasis? Nat Med 9:822–823

    Article  PubMed  CAS  Google Scholar 

  94. Grepin R, Pages G (2010) Molecular mechanisms of resistance to tumour anti-angiogenic strategies. J Oncol 2010:835680

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Stem Cell Biology & Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA

    Gloria Bonuccelli & Michael P. Lisanti

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  1. Gloria Bonuccelli
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  2. Michael P. Lisanti
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Correspondence to Gloria Bonuccelli or Michael P. Lisanti .

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Editors and Affiliations

  1. Kimmel Cancer Center, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Isabelle Mercier

  2. Bluemle Bldg, Rm 939, Department of Stem Cell Biology and Rege, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Jean-François Jasmin

  3. Kimmel Cancer Center, Thomas Jefferson University, S. 10th Street 233, Philadelphia, 19107, Pennsylvania, USA

    Michael P. Lisanti

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Bonuccelli, G., Lisanti, M.P. (2012). Caveolin-1 and Breast Cancer. In: Mercier, I., Jasmin, JF., Lisanti, M. (eds) Caveolins in Cancer Pathogenesis, Prevention and Therapy. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1001-0_7

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  • DOI: https://doi.org/10.1007/978-1-4614-1001-0_7

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