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Cripto haploinsufficiency affects in vivo colon tumor development

Colorectal cancer is one of the most common and aggressive cancers arising from alterations in various signaling pathways, such as the WNT, RAS-MAPK, PI3K and transforming growth factor-β (TGF-β) pathways. Cripto (also called Teratocarcinoma-derived growth factor), the original member of the vertebr...

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Autores principales: GIORGIO, EMILIA, LIGUORO, ANNAMARIA, D’ORSI, LUCA, MANCINELLI, SARA, BARBIERI, ANTONIO, PALMA, GIUSEPPE, ARRA, CLAUDIO, LIGUORI, GIOVANNA L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079161/
https://www.ncbi.nlm.nih.gov/pubmed/24805056
http://dx.doi.org/10.3892/ijo.2014.2412
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author GIORGIO, EMILIA
LIGUORO, ANNAMARIA
D’ORSI, LUCA
MANCINELLI, SARA
BARBIERI, ANTONIO
PALMA, GIUSEPPE
ARRA, CLAUDIO
LIGUORI, GIOVANNA L.
author_facet GIORGIO, EMILIA
LIGUORO, ANNAMARIA
D’ORSI, LUCA
MANCINELLI, SARA
BARBIERI, ANTONIO
PALMA, GIUSEPPE
ARRA, CLAUDIO
LIGUORI, GIOVANNA L.
author_sort GIORGIO, EMILIA
collection PubMed
description Colorectal cancer is one of the most common and aggressive cancers arising from alterations in various signaling pathways, such as the WNT, RAS-MAPK, PI3K and transforming growth factor-β (TGF-β) pathways. Cripto (also called Teratocarcinoma-derived growth factor), the original member of the vertebrate EGF-CFC family, plays a key role in all of these pathways and is deeply involved in early embryo development and cancer progression. The role of Cripto in colon and breast cancer, in particular, has been investigated, as it is still not clearly understood. In this article, we provide the first in vivo functional evidence of a role of Cripto in colon cancer development. We analyzed the effect of Cripto haploinsufficiency on colon tumor formation by treating Cripto heterozygous mice with the colonotropic carcinogen azoxymethane (AOM). Of note, in our model system, Cripto haploinsufficiency increased tumorigenesis. Moreover, we revealed a correlation between the differential AOM response found in wt and Cripto(+/−) mice and the expression levels of glucose regulated protein-78 (Grp78), a heat shock protein required for Cripto signaling pathways. We hypothesize that the balance between Cripto and Grp78 expression levels might be crucial in cancer development and may account for the increased tumorigenesis in Cripto heterozygous mice. In summary, our results highlight the heterogeneous effect of Cripto on tumorigenesis and the consequent high level of complexity in the Cripto regulatory pathway, whose imbalance causes tumors.
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spelling pubmed-40791612014-07-02 Cripto haploinsufficiency affects in vivo colon tumor development GIORGIO, EMILIA LIGUORO, ANNAMARIA D’ORSI, LUCA MANCINELLI, SARA BARBIERI, ANTONIO PALMA, GIUSEPPE ARRA, CLAUDIO LIGUORI, GIOVANNA L. Int J Oncol Articles Colorectal cancer is one of the most common and aggressive cancers arising from alterations in various signaling pathways, such as the WNT, RAS-MAPK, PI3K and transforming growth factor-β (TGF-β) pathways. Cripto (also called Teratocarcinoma-derived growth factor), the original member of the vertebrate EGF-CFC family, plays a key role in all of these pathways and is deeply involved in early embryo development and cancer progression. The role of Cripto in colon and breast cancer, in particular, has been investigated, as it is still not clearly understood. In this article, we provide the first in vivo functional evidence of a role of Cripto in colon cancer development. We analyzed the effect of Cripto haploinsufficiency on colon tumor formation by treating Cripto heterozygous mice with the colonotropic carcinogen azoxymethane (AOM). Of note, in our model system, Cripto haploinsufficiency increased tumorigenesis. Moreover, we revealed a correlation between the differential AOM response found in wt and Cripto(+/−) mice and the expression levels of glucose regulated protein-78 (Grp78), a heat shock protein required for Cripto signaling pathways. We hypothesize that the balance between Cripto and Grp78 expression levels might be crucial in cancer development and may account for the increased tumorigenesis in Cripto heterozygous mice. In summary, our results highlight the heterogeneous effect of Cripto on tumorigenesis and the consequent high level of complexity in the Cripto regulatory pathway, whose imbalance causes tumors. D.A. Spandidos 2014-04-30 /pmc/articles/PMC4079161/ /pubmed/24805056 http://dx.doi.org/10.3892/ijo.2014.2412 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
GIORGIO, EMILIA
LIGUORO, ANNAMARIA
D’ORSI, LUCA
MANCINELLI, SARA
BARBIERI, ANTONIO
PALMA, GIUSEPPE
ARRA, CLAUDIO
LIGUORI, GIOVANNA L.
Cripto haploinsufficiency affects in vivo colon tumor development
title Cripto haploinsufficiency affects in vivo colon tumor development
title_full Cripto haploinsufficiency affects in vivo colon tumor development
title_fullStr Cripto haploinsufficiency affects in vivo colon tumor development
title_full_unstemmed Cripto haploinsufficiency affects in vivo colon tumor development
title_short Cripto haploinsufficiency affects in vivo colon tumor development
title_sort cripto haploinsufficiency affects in vivo colon tumor development
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079161/
https://www.ncbi.nlm.nih.gov/pubmed/24805056
http://dx.doi.org/10.3892/ijo.2014.2412
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