Cripto-1 Overexpression Leads to Enhanced Invasiveness and Resistance to Anoikis in Human MCF-7 Breast Cancer Cells

Nicola Normanno*, Antonella De Luca, Caterina Bianco, Monica R. Maiello, Maria V. Carriero, Aasia Rehman, Christian Wechselberger, Claudio Arra, Luigi Strizzi, Michele Sanicola, David S. Salomon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Cripto-1 (CR-1) is an epidermal growth factor (EGF)-CFC protein that has been shown to signal through nodal/Alk-4, PI3K/Akt, and/or ras/raf/MEK/MAPK pathways in mammalian cells, and that is frequently expressed in human primary breast carcinomas. In the present study, the human estrogen receptor positive, MCF-7 breast cancer cell line, that expresses low levels of endogenous CR-1, was transfected with a CR-1 expression vector. MCF-7 CR-1 cells expressed high levels of a 25 kDa recombinant CR-1 protein that was not detected in MCF-7 cells transfected with a control vector (MCF-7 neo). Overexpression of CR-1 did not induce an estrogen independent phenotype in MCF-7 cells. In fact, MCF-7 CR-1 cells showed a response to exogenous estrogens that was similar to MCF-7 neo cells, and failed to grow in immunosuppressed mice in absence of estrogen stimulation. However, MCF-7 CR-1 cells showed a rate of proliferation in serum free conditions, and an ability to form colonies in soft-agar that were higher as compared with MCF-7 neo cells. More importantly, overexpression of CR-1 enhanced the resistance to anoikis and the invasion ability of MCF-7 cells. MCF-7 CR-1 cells showed levels of activation of both Akt and Smad-2 that were significantly higher as compared with MCF-7 neo. These findings suggest that CR-1 overexpression might be associated with the progression towards a more aggressive phenotype in breast carcinoma, through the activation of both Akt and Smad-2 signalling pathways.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalJournal of Cellular Physiology
Volume198
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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