Regulation of Cripto-1 signaling and biological activity by caveolin-1 in mammary epithelial cells

Caterina Bianco, Luigi Strizzi, Mario Mancino, Kazuhide Watanabe, Monica Gonzales, Shin Hamada, Ahmed Raafat, Lawson Sahlah, Cindy Chang, Federica Sotgia, Nicola Normanno, Michael Lisanti, David S. Salomon

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Human and mouse Cripto-1 (CR-1/Cr-1) proteins play an important role in mammary gland development and tumorigenesis. In this study, we examined the relationship between Cripto-1 and caveolin-1 (Cav-1), a membrane protein that acts as a tumor suppressor in the mammary gland. Cripto-1 was found to interact with Cav-1 in COS7 cells and mammary epithelial cells. Using EpH4 mouse mammary epithelial cells expressing Cr-1 (EpH4 Cr-1) or Cr-1 and Cav-1 (EpH4 Cr-1/Cav-1), we demonstrate that Cav-1 expression markedly reduced the ability of Cr-1 to enhance migration, invasion, and formation of branching structures in EpH4 Cr-1/Cav-1 cells as compared to EpH4 Cr-1 cells. Furthermore, coexpression of Cav-1 together with Cr-1 in EpH4 Cr-1/Cav-1 cells inhibited Cr-1-mediated activation of c-src and mitogen-activated protein kinase signaling pathways. Conversely, primary mammary epithelial cells isolated from Cav-1 null -/-/mouse mammary tumor virus-CR-1 transgenic animals showed enhanced motility and activation of mitogen-activated protein kinase and c-src as compared to Cav-1+/+/CR-1 mammary cells. Finally, mammary tumors derived from mouse mammary tumor virus-CR-1 mice showed a dramatic reduction of Cav-1 expression as compared to mammary tissue from normal FVB/N mice, suggesting that in vivo Cav-1 is down-regulated during the process of CR-1-mediated mammary tumorigenesis.

Original languageEnglish
Pages (from-to)345-357
Number of pages13
JournalAmerican Journal of Pathology
Volume172
Issue number2
DOIs
Publication statusPublished - 2008 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Regulation of Cripto-1 signaling and biological activity by caveolin-1 in mammary epithelial cells'. Together they form a unique fingerprint.

  • Cite this

    Bianco, C., Strizzi, L., Mancino, M., Watanabe, K., Gonzales, M., Hamada, S., Raafat, A., Sahlah, L., Chang, C., Sotgia, F., Normanno, N., Lisanti, M., & Salomon, D. S. (2008). Regulation of Cripto-1 signaling and biological activity by caveolin-1 in mammary epithelial cells. American Journal of Pathology, 172(2), 345-357. https://doi.org/10.2353/ajpath.2008.070696