Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer

Maria C. Rangel, Hideaki Karasawa, Nadia P. Castro, Tadahiro Nagaoka, David S. Salomon, Caterina Bianco

Research output: Contribution to journalReview article

69 Citations (Scopus)

Abstract

Epithelial-to-mesenchymal transition (EMT) is a critical multistep process that converts epithelial cells to more motile and invasive mesenchymal cells, contributing to body patterning and morphogenesis during embryonic development. In addition, both epithelial plasticity and increased motility and invasiveness are essential for the branching morphogenesis that occurs during development of the mammary gland and during tumor formation, allowing cancer cells to escape from the primary tumor. Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic (EGF/CFC) gene family, together with the transforming growth factor (TGF)-β family ligand Nodal, regulates both cell movement and EMT during embryonic development. During postnatal development, Cripto-1 regulates the branching morphogenesis of the mouse mammary gland and enhances both the invasive and migratory properties of mammary epithelial cells in vitro. Furthermore, transgenic mouse models have shown that Cripto-1 promotes the formation of mammary tumors that display properties of EMT, including the down-regulation of the cell surface adherens junctional protein E-cadherin and the up-regulation of mesenchymal markers, such as vimentin, N-cadherin, and Snail. Interestingly, Cripto-1 is enriched in a subpopulation of embryonal, melanoma, prostate, and pancreatic cancer cells that possess stem-like characteristics. Therefore, Cripto-1 may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program.

Original languageEnglish
Pages (from-to)2188-2200
Number of pages13
JournalAmerican Journal of Pathology
Volume180
Issue number6
DOIs
Publication statusPublished - 01-06-2012

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Epithelial-Mesenchymal Transition
Morphogenesis
Cadherins
Human Mammary Glands
Neoplasms
Embryonic Development
Body Patterning
Epithelial Cells
Tumor Escape
Neoplastic Stem Cells
Germ Cell and Embryonal Neoplasms
Transforming Growth Factors
Vimentin
Pancreatic Neoplasms
Epidermal Growth Factor
Transgenic Mice
Cell Movement
Melanoma
Prostatic Neoplasms
Breast

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Rangel, Maria C. ; Karasawa, Hideaki ; Castro, Nadia P. ; Nagaoka, Tadahiro ; Salomon, David S. ; Bianco, Caterina. / Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. In: American Journal of Pathology. 2012 ; Vol. 180, No. 6. pp. 2188-2200.
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Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. / Rangel, Maria C.; Karasawa, Hideaki; Castro, Nadia P.; Nagaoka, Tadahiro; Salomon, David S.; Bianco, Caterina.

In: American Journal of Pathology, Vol. 180, No. 6, 01.06.2012, p. 2188-2200.

Research output: Contribution to journalReview article

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