Cripto-1: an extracellular protein - connecting the sequestered biological dots.

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.