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Review
. 2021 Aug 27;22(17):9280.
doi: 10.3390/ijms22179280.

Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells

Hilal Arnouk  1   2   3   4 , Gloria Yum  2 , Dean Shah  3   5
Affiliations
Review

Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells

Hilal Arnouk et al. Int J Mol Sci. .

Abstract

Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1's role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients.

Keywords: Cripto-1; EMT; biomarker; breast cancer; cancer stem cells; epithelial to mesenchymal transition; melanoma; metastasis; therapeutic target; tumor progression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Epithelial to Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET).
Figure 2
Figure 2
Upregulated and Downregulated Proteins in EMT.
See this image and copyright information in PMC

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