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Cripto/GRP78 modulation of the TGF-β pathway in development and oncogenesis

Peter C Gray1, Wylie Vale

  • 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
PubMed

Insights

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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