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

Klauzinska, M.; Bertolette, D.; Tippireddy, S.; Strizzi, L.; Gray, P. C.; Gonzales, M.; Duroux, M.; Ruvo, M.; Wechselberger, C.; Castro, N. P.; Rangel, M. C.; Foca, A.; Sandomenico, A.; Hendrix, M. J.; Salomon, D.; Cuttitta, F.

Connect Tissue Res. 2015 Sep 4; 56(5):364-80

Abstract

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.

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