Skip to main content
SpringerLink
Log in

Caveolin-1 and Breast Cancer: A New Clinical Perspective

  • Chapter
Book cover Caveolins and Caveolae

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 729))

Abstract

The current chapter focuses on the role of Caveolin-1 (Cav-1) in cellular growth with an emphasis on its implication in breast cancer initiation, progression, clinical prognosis and as a potential therapeutic target. The role of Cav-1 as a tumor suppressor in breast cancer has emerged in the past few years, with dual functions on both cancer epithelium as well as the cancer stroma. Its multiple functions as a regulator of estrogen signaling and kinase activity and its newly found role as an important factor controlling the dynamic relationship between cancer epithelia and stroma position Cav-1 as a new therapeutic target for the treatment of breast cancer.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Oka N, Yamamoto M, Schwencke C et al. Caveolin interaction with protein kinase C: Isoenzyme-dependent regulation of kinase activity by the caveolin-scaffolding domain peptide. J Biol Chem 1997; 272:33416–33421.

    Article  PubMed  CAS  Google Scholar 

  2. Couet J, Li S, Okamoto T et al. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 1997; 272:6525–6533.

    Article  PubMed  CAS  Google Scholar 

  3. Okamoto T, Schlegel A, Scherer PE et al. Caveolins, A family of scaffolding proteins for organizing “pre-assembled signaling complexes” at the plasma membrane. J Biol Chem (Mini-review) 1998; 273:5419–5422.

    Article  CAS  Google Scholar 

  4. Engelman JA, Zhang XL, Galbiati F et al. Molecular Genetics of the Caveolin Gene Family: Implications for Human Cancers, Diabetes, Alzheimer’s Disease, and Muscular Dystrophy. Am J Hum Genetics 1998; 63:1578–1587.

    Article  CAS  Google Scholar 

  5. Smart EJ, Graf GA, McNiven MA et al. Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 1999; 19:7289–7304.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Engelman JA, Wykoff CC, Yasuhara S et al. Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates anchorage-independent growth. J Biol Chem 1997; 272:16374–16381.

    Article  PubMed  CAS  Google Scholar 

  8. Galbiati F, Volonte D, Engelman JA et al. Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade. EMBO J 1998; 17:6633–6648.

    Article  PubMed  CAS  Google Scholar 

  9. Engelman JA, Zhang XL, Galbiati F et al. Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1,-2 and-3). Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/7q31). FEBS Lett 1998; 429:330–336.

    Article  PubMed  CAS  Google Scholar 

  10. Sotgia F, Williams TM, Schubert W et al. Caveolin-1 deficiency (-/-) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. Am J Pathol 2006; 168:292–309.

    Article  PubMed  CAS  Google Scholar 

  11. Fiucci G, Ravid D, Reich R et al. Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene 2002; 21:2365–2375.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang X, Shen P, Coleman M et al. Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17beta-estradiol-stimulated mammary tumorigenesis. Anticancer Res 2005; 25:369–375.

    PubMed  Google Scholar 

  13. Zhang W, Razani B, Altschuler Y et al. 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 2000; 275:20717–20725.

    Article  PubMed  CAS  Google Scholar 

  14. Lee SW, Reimer CL, Oh P et al. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene 1998; 16:1391–1397.

    Article  PubMed  CAS  Google Scholar 

  15. Wu P, Wang X, Li F et al. Growth suppression of MCF-7 cancer cell-derived xenografts in nude mice by caveolin-1. Biochem Biophys Res Commun 2008; 376:215–220.

    Article  PubMed  CAS  Google Scholar 

  16. Lee H, Park DS, Razani B et al. 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 2002; 161:1357–1369.

    Article  PubMed  CAS  Google Scholar 

  17. Williams TM, Medina F, Badano I et al. 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 2004; 279:51630–51646.

    Article  PubMed  CAS  Google Scholar 

  18. Bonuccelli G, Casimiro MC, Sotgia F et al. 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 2009; 174:1650–1662.

    Article  PubMed  CAS  Google Scholar 

  19. Hayashi K, Matsuda S, Machida K et al. Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Res 2001; 61:2361–2364.

    PubMed  CAS  Google Scholar 

  20. Mercier I, Bryant KG, Sotgia F et al. Using Caveolin-1 epithelial immunostaining patterns to stratify human breast cancer patients and predict the Caveolin-1 (P132L) mutation. Cell Cycle 2009; 8(9):1396–401.

    Article  PubMed  CAS  Google Scholar 

  21. Li T, Sotgia F, Vuolo MA et al. Caveolin-1 mutations in human breast cancer: Functional association with estrogen receptor alpha-positive status. Am J Pathol 2006; 168:1998–2013.

    Article  PubMed  CAS  Google Scholar 

  22. Clemons M, Goss P. Estrogen and the risk of breast cancer. N Engl J Med 2001; 344:276–285.

    Article  PubMed  CAS  Google Scholar 

  23. Lacroix M, Toillon RA, Leclercq G. Stable ‘portrait’ of breast tumors during progression: data from biology, pathology and genetics. Endocr Relat Cancer 2004; 11:497–522.

    Article  PubMed  CAS  Google Scholar 

  24. Foster JS, Henley DC, Ahamed S et al. Estrogens and cell-cycle regulation in breast cancer. Trends Endocrinol Metab 2001; 12:320–327.

    Article  PubMed  CAS  Google Scholar 

  25. Mercier I, Casimiro MC, Zhou J et al. Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of DCIS-like mammary lesions. Am J Pathol 2009; 174:1172–1190.

    Article  PubMed  CAS  Google Scholar 

  26. Zou W, McDaneld L, Smith LM. Caveolin-1 haploinsufficiency leads to partial transformation of human breast epithelial cells. Anticancer Res 2003; 23:4581–4586.

    PubMed  CAS  Google Scholar 

  27. Olewniczak S, Chosia M, Kwas A et al. Angiogenesis and some prognostic parameters of invasive ductal breast carcinoma in women. Pol J Pathol 2002; 53:183–188.

    PubMed  Google Scholar 

  28. Jung DJ, Na SY, Na DS et al. Molecular cloning and characterization of CAPER, a novel coactivator of activating protein-1 and estrogen receptors. J Biol Chem 2002; 277:1229–1234.

    Article  PubMed  CAS  Google Scholar 

  29. Itahana K, Bhat KP, Jin A et al. Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell 2003; 12:1151–1164.

    Article  PubMed  CAS  Google Scholar 

  30. Orimo A, Gupta PB, Sgroi DC et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121:335–348.

    Article  PubMed  CAS  Google Scholar 

  31. Orimo A, Weinberg RA. Stromal fibroblasts in cancer: A novel tumor-promoting cell type. Cell Cycle 2006; 5:1597–1601.

    Article  PubMed  CAS  Google Scholar 

  32. Shimoda M, Mellody KT, Orimo A. Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol 2010; 21(1):19–25.

    Article  PubMed  CAS  Google Scholar 

  33. Ostman A, Augsten M. Cancer-associated fibroblasts and tumor growth—bystanders turning into key players. Curr Opin Genet Dev 2009; 19:67–73.

    Article  PubMed  Google Scholar 

  34. Ryan GB, Cliff WJ, Gabbiani G et al. Myofibroblasts in human granulation tissue. Hum Pathol 1974; 5:55–67.

    Article  PubMed  CAS  Google Scholar 

  35. Oliver N, Babu M, Diegelmann R. Fibronectin gene transcription is enhanced in abnormal wound healing. J Invest Dermatol 1992; 99:579–586.

    Article  PubMed  CAS  Google Scholar 

  36. Babu M, Diegelmann R, Oliver N. Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing. Mol Cell Biol 1989; 9:1642–1650.

    PubMed  CAS  Google Scholar 

  37. Pavlides S, Tsirigos A, Migneco G et al. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 2010; 9(21):4297–306.

    Article  PubMed  Google Scholar 

  38. Martinez-Outschoorn UE, Balliet RM, Rivadeneira et al. 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 1010; 9(16):3256–76.

    Article  Google Scholar 

  39. Mercier I, Casimiro MC, Wang C et al. 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 2008; 7:1212–1225.

    Article  PubMed  CAS  Google Scholar 

  40. Witkiewicz AK, Dasgupta A, Sotgia F et al. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol 2009; 174:2023–2034.

    Article  PubMed  CAS  Google Scholar 

  41. Witkiewicz AK, Dasgupta A, Sammons S et al. Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers. Cancer Biol Ther 2010; 10(2):135–43

    Article  PubMed  Google Scholar 

  42. Witkiewicz AK, Dasgupta A, Nguyen KH et al. Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther 2009; 8:1071–1079.

    Article  PubMed  CAS  Google Scholar 

  43. Kundu M, Thompson CB. Autophagy: Basic principles and relevance to disease. Annu Rev Pathol 2008; 3:427-455. 44. Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009; 335:1–32.

    Article  Google Scholar 

  44. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009; 43:67–93.

    Article  PubMed  CAS  Google Scholar 

  45. Di Vizio D, Morello M, Sotgia F et al. An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation. Cell Cycle 2009; 8:2420–2424.

    Article  PubMed  Google Scholar 

  46. Martinez-Outschoorn UE, Trimmer C, Lin Z et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cell Cycle 2010; 9(17):3515–3533.

    Article  PubMed  CAS  Google Scholar 

  47. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S et al. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: A simple solution to the autophagy paradox. Cell Cycle 2010; 9(21):4297–306

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Isabelle Mercier & Michael P. Lisanti

Authors
  1. Isabelle Mercier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael P. Lisanti
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Jean-François Jasmin PhD

  2. Departments of Cancer Biology, and Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Philippe G. Frank PhD  & Michael P. Lisanti MD, PhD  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Mercier, I., Lisanti, M.P. (2012). Caveolin-1 and Breast Cancer: A New Clinical Perspective. In: Jasmin, JF., Frank, P.G., Lisanti, M.P. (eds) Caveolins and Caveolae. Advances in Experimental Medicine and Biology, vol 729. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1222-9_6

Download citation

Publish with us

Policies and ethics

Search

Navigation