Cripto Binds Transforming Growth Factor Beta (TGF-beta) and Inhibits TGF-beta Signaling

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Oct 13

PMID 17030617

Citations 43

Authors

Peter C Gray

Gidi Shani

Kevin Aung

Jonathan Kelber

Wylie Vale

Affiliations

Soon will be listed here.

Abstract

Cripto is a developmental oncoprotein and a member of the epidermal growth factor-Cripto, FRL-1, Cryptic family of extracellular signaling molecules. In addition to having essential functions during embryogenesis, Cripto is highly expressed in tumors and promotes tumorigenesis. During development, Cripto acts as an obligate coreceptor for transforming growth factor beta (TGF-beta) ligands, including nodals, growth and differentiation factor 1 (GDF1), and GDF3. As an oncogene, Cripto is thought to promote tumor growth via mechanisms including activation of mitogenic signaling pathways and antagonism of activin signaling. Here, we provide evidence supporting a novel mechanism in which Cripto inhibits the tumor suppressor function of TGF-beta. Cripto bound TGF-beta and reduced the association of TGF-beta with its type I receptor, TbetaRI. Consistent with its ability to block receptor assembly, Cripto suppressed TGF-beta signaling in multiple cell types and diminished the cytostatic effects of TGF-beta in mammary epithelial cells. Furthermore, targeted disruption of Cripto expression by use of small inhibitory RNA enhanced TGF-beta signaling, indicating that endogenous Cripto plays a role in restraining TGF-beta responses.

Citing Articles

Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

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CRIPTO's multifaceted role in driving aggressive prostate cancer unveiled by in vivo, organoid, and patient data.

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Oncofetal Protein CRIPTO Is Involved in Wound Healing and Fibrogenesis in the Regenerating Liver and Is Associated with the Initial Stages of Cardiac Fibrosis.

Karkampouna S, van der Helm D, Scarpa M, van Hoek B, Verspaget H, Goumans M Cells. 2021; 10(12).

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Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.

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Liver-specific over-expression of Cripto-1 in transgenic mice promotes hepatocyte proliferation and deregulated expression of hepatocarcinogenesis-related genes and signaling pathways.

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