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.
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Malgorzata
M
Klauzinska
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Daniel
D
Bertolette
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Sudhamsh
S
Tippireddy
b Department of Pathology , Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine , Chicago , IL , USA .
Luigi
L
Strizzi
c Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies , La Jolla , CA , USA .
Peter C
PC
Gray
d Office of Research Operations, Office of the Director, Center for Cancer Research, National Cancer Institute , Bethesda , MD , USA .
Monica
M
Gonzales
e Laboratory of Cancer Biology , Biomedicine Group, Department of Health Science and Technology, Aalborg University , Aalborg East , Denmark .
Meg
M
Duroux
f CIRPeB, University of Naples Federico II , Napoli , Italy .|g Istituto di Biostrutture e Bioimmagini del CRN , Napoli , Italy .
Menotti
M
Ruvo
h Greiner Bio-One Diagnostics GmbH, Rainbach im Mühlkreis , Austria .
Christian
C
Wechselberger
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Nadia P
NP
Castro
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Maria Cristina
MC
Rangel
g Istituto di Biostrutture e Bioimmagini del CRN , Napoli , Italy .|i Dipartimento di Farmacia, University of Naples Federico II , Napoli , Italy , and.
Annalia
A
Focà
f CIRPeB, University of Naples Federico II , Napoli , Italy .
Annamaria
A
Sandomenico
j Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
Mary J C
MJ
Hendrix
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
David
D
Salomon
a Tumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA .
Frank
F
Cuttitta
D001323:Autoantibodies / Q000276:immunology; D004815:Epidermal Growth Factor / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001323:Autoantibodies; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor
Autoantibodies; Cripto-1; Cripto-1 detection; drug discovery; inflammation