Tumor Biology

, Volume 37, Issue 2, pp 2015–2021 | Cite as

∆Np73beta induces caveolin-1 in human non-small cell lung cancer cell line H1299

  • Elisa Caiola
  • Eleonora Marrazzo
  • Simona Alesci
  • Massimo Broggini
  • Mirko Marabese
Original Article


Caveolins have recently attracted attention for their possible involvement in signal transduction. Their role in cancer is debated, being reported both a suppressive and oncogenic role in different experimental conditions. Caveolin-1 is regulated by the tumor suppressor p53 which is able to bind its promoter and activate transcription. We had previous evidences indicating that a specific p73 isoform, namely ∆Np73β, when overexpressed in NCI-H1299 induced growth arrest and cell death. By gene expression analysis in cell transiently overexpressed with ∆Np73β, a strong induction of caveolin-1 was found. Caveolin was induced both at mRNA and protein level, and we characterised the promoter sequence of the gene encoding for caveolin-1 and found that the promoter region containing the putative p53 (and hence p73) binding sequence was responsive to ∆Np73β, but not to ∆Np73α and ∆Np73γ which do not induce growth arrest as ∆Np73β does. A reduction in cell adhesion was observed in ∆Np73β overexpressing cells, again supporting a possible role of caveolins in determining these effects. By using specific siRNA directed against human caveolin-1, we could not however antagonize the effects induced by ∆Np73β. Although caveolin-1 represents one of the genes whose expression is strongly activated by ∆Np73β, we could not define a role of caveolin-1 as a mediator of ∆Np73β associated growth arrest. It could well be that the expression of caveolin-1 is able to mediate other activities of ∆Np73β, and studies are in progress to determine whether its expression is mainly associated to metastatic spread.


Caveolin-1 cav-1 p73 ∆Np73 Lung NSCLC 



The generous contribution of Alpe Burki-Macugnaga is gratefully acknowledged. The authors would like to dedicate this work to the memory of Dr. Maria Antonietta Sabatino, a very talented and motivated scientist, as well as a very good friend, who unfortunately passed away at very young age.

Conflicts on interest


Supplementary material

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High resolution image (TIFF 192 kb)


  1. 1.
    Fridolfsson HN, Roth DM, Insel PA, Patel HH. Regulation of intracellular signaling and function by caveolin. FASEB J. 2014;28(9):3823–31.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hehlgans S, Cordes N. Caveolin-1: an essential modulator of cancer cell radio-and chemoresistance. Am J Cancer Res. 2011;1:521–30.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Chidlow Jr JH, Sessa WC. Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation. Cardiovasc Res. 2010;86:219–25.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lin MI, Yu J, Murata T, Sessa WC. Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Res. 2007;67:2849–56.CrossRefPubMedGoogle Scholar
  5. 5.
    Galbiati F, Volonte D, Engelman JA, Watanabe G, Burk R, Pestell RG, et al. Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 map kinase cascade. EMBO J. 1998;17:6633–48.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cantiani L, Manara MC, Zucchini C, De Sanctis P, Zuntini M, Valvassori L, et al. Caveolin-1 reduces osteosarcoma metastases by inhibiting c-src activity and met signaling. Cancer Res. 2007;67:7675–85.CrossRefPubMedGoogle Scholar
  7. 7.
    Ho CC, Huang PH, Huang HY, Chen YH, Yang PC, Hsu SM. Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol. 2002;161:1647–56.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Li M, Chen H, Diao L, Zhang Y, Xia C, Yang F. Caveolin-1 and vegf-c promote lymph node metastasis in the absence of intratumoral lymphangiogenesis in non-small cell lung cancer. Tumori. 2010;96:734–43.PubMedGoogle Scholar
  9. 9.
    Wang R, Li Z, Guo H, Shi W, Xin Y, Chang W, et al. Caveolin 1 knockdown inhibits the proliferation, migration and invasion of human breast cancer bt474 cells. Mol Med Rep. 2014;9:1723–8.PubMedGoogle Scholar
  10. 10.
    Yu X, Riley T, Levine AJ. The regulation of the endosomal compartment by p53 the tumor suppressor gene. FEBS J. 2009;276:2201–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Marrazzo E, Marchini S, Tavecchio M, Alberio T, Previdi S, Erba E, et al. The expression of the deltanp73beta isoform of p73 leads to tetraploidy. Eur J Cancer. 2009;45:443–53.CrossRefPubMedGoogle Scholar
  12. 12.
    Vikhanskaya F, Clerico L, Valenti M, Stanzione MS, Broggini M, Parodi S, et al. Mechanism of resistance to cisplatin in a human ovarian-carcinoma cell line selected for resistance to doxorubicin: Possible role of p53. Int J Cancer. 1997;72:155–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Marabese M, Mazzoletti M, Vikhanskaya F, Broggini M. Htra2 enhances the apoptotic functions of p73 on bax. Cell Death Differ. 2008;15:849–58.CrossRefPubMedGoogle Scholar
  14. 14.
    Marabese M, Vikhanskaya F, Broggini M. P73: a chiaroscuro gene in cancer. Eur J Cancer. 2007;43:1361–72.CrossRefPubMedGoogle Scholar
  15. 15.
    Nunez-Wehinger S, Ortiz RJ, Diaz N, Diaz J, Lobos-Gonzalez L, Quest AF. Caveolin-1 in cell migration and metastasis. Curr Mol Med. 2014;14:255–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang H, Su L, Muller S, Tighiouart M, Xu Z, Zhang X, et al. Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma. Br J Cancer. 2008;99:1684–94.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chiu WT, Lee HT, Huang FJ, Aldape KD, Yao J, Steeg PS, et al. Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition. Cancer Res. 2011;71:4932–43.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Quann K, Gonzales DM, Mercier I, Wang C, Sotgia F, Pestell RG, et al. Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide. Cell Cycle. 2013;12:1510–20.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Brodie SA, Lombardo C, Li G, Kowalski J, Gandhi K, You S, et al. Aberrant promoter methylation of caveolin-1 is associated with favorable response to taxane-platinum combination chemotherapy in advanced nsclc. PLoS One. 2014;9:e107124.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pancotti F, Roncuzzi L, Maggiolini M, Gasperi-Campani A. Caveolin-1 silencing arrests the proliferation of metastatic lung cancer cells through the inhibition of stat3 signaling. Cell Signal. 2012;24:1390–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Salem AF, Bonuccelli G, Bevilacqua G, Arafat H, Pestell RG, Sotgia F, et al. Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous e-cadherin via suppression of the epithelial-mesenchymal transition. Cell Cycle. 2011;10:3692–700.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chunhacha P, Chanvorachote P. Roles of caveolin-1 on anoikis resistance in non small cell lung cancer. Int J Physiol Pathophysiol Pharmacol. 2012;4:149–55.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Chunhacha P, Pongrakhananon V, Rojanasakul Y, Chanvorachote P. Caveolin-1 regulates mcl-1 stability and anoikis in lung carcinoma cells. Am J Physiol Cell Physiol. 2012;302:C1284–92.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Halim H, Luanpitpong S, Chanvorachote P. Acquisition of anoikis resistance up-regulates caveolin-1 expression in human non-small cell lung cancer cells. Anticancer Res. 2012;32:1649–58.PubMedGoogle Scholar
  25. 25.
    Wang Z, Wang N, Li W, Liu P, Chen Q, Situ H, et al. Caveolin-1 mediates chemoresistance in breast cancer stem cells via beta-catenin/abcg2 signaling pathway. Carcinogenesis. 2014;35:2346–56.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Laboratory of Molecular PharmacologyIRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

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