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Published on: October 27, 2020
Cripto/GRP78 modulation of the TGF-β pathway in development and oncogenesis
1Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, United States. gray@salk.edu
FEBS Letters
|February 7, 2012
Summary
Cripto, a signaling protein, regulates cell functions and cancer. This review identifies GRP78 as a key co-receptor for Cripto, impacting stem cell and cancer biology.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Cancer Biology
Background:
- Cripto is a GPI-anchored protein regulating cell survival, proliferation, differentiation, and migration.
- It acts as a co-receptor for TGF-β ligands like Nodal, GDF1, and GDF3, while modulating others.
- Secreted Cripto activates Src, ras/raf/MAPK, and PI3K/Akt pathways through unclear mechanisms.
Purpose of the Study:
- To review the biological roles and signaling mechanisms of Cripto.
- To highlight the identification of GRP78 as a cell surface receptor/co-factor for Cripto.
- To discuss Cripto/GRP78 signaling in stem cells and cancer.
Main Methods:
- Literature review of Cripto's biological roles and signaling.
- Identification of GRP78 as a Cripto co-receptor.
- Analysis of Cripto/GRP78 signaling pathways.
Main Results:
- Cripto signaling is modulated by GRP78, a 78 kDa glucose-regulated protein.
- GRP78 is essential for Cripto signaling through both TGF-β and Src/MAPK/PI3K pathways.
- Cripto/GRP78 signaling influences normal somatic stem cells and their tumorigenic counterparts.
Conclusions:
- GRP78 is a crucial cell surface receptor/co-factor for Cripto.
- Cripto/GRP78 signaling plays a significant role in stem cell regulation and tumorigenesis.
- Further research into Cripto/GRP78 pathways may offer therapeutic targets.
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