Cripto-1: an extracellular protein – connecting the sequestered biological dots. (3rd September 2015)

• Record Type: Journal Article
• Authors: Klauzinska, Malgorzata; Bertolette, Daniel; Tippireddy, Sudhamsh; Strizzi, Luigi; Gray, Peter C.; Gonzales, Monica; Duroux, Meg; Ruvo, Menotti; Wechselberger, Christian; Castro, Nadia P.; Rangel, Maria Cristina; Focà, Annalia; Sandomenico, Annamaria; Hendrix, Mary J. C.; Salomon, David; Cuttitta, Frank
• Is Part Of: Connective tissue research. Volume 56:Number 5(2015:Oct.)
• Page Start: 364
• Page End: 380
• Publication Date: 2015-09-03
• Subjects: Autoantibodies -- Cripto-1 -- Cripto-1 detection -- drug discovery -- inflammation; Connective tissues -- Periodicals; 616.770072
• DOI: 10.3109/03008207.2015.1077239
• Languages: English
• ISSNs: 0300-8207

Abstract

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.