Cripto-1: An extracellular protein - Connecting the sequestered biological dots

Malgorzata Klauzinska*, Daniel Bertolette, Sudhamsh Tippireddy, Luigi Strizzi, Peter C. Gray, Monica Gonzales, Meg Duroux, Menotti Ruvo, Christian Wechselberger, Nadia P. Castro, Maria Cristina Rangel, Annalia Focà, Annamaria Sandomenico, Mary J.C. Hendrix, David Salomon, Frank Cuttitta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways. In addition, there are several naturally occurring binding partner proteins (BPPs) for CR-1 that can either agonize or antagonize its bioactivity. We will review the collective role of CR-1 as an extracellular protein, discuss caveats to consider in developing a quantitation assay, define possible mechanistic avenues applicable for drug discovery, and report on our experimental approaches to overcome these problematic issues.

Original languageEnglish (US)
Pages (from-to)364-380
Number of pages17
JournalConnective tissue research
Issue number5
StatePublished - Sep 3 2015


  • Autoantibodies
  • Cripto-1
  • Cripto-1 detection
  • drug discovery
  • inflammation

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

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