Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 31-40 |
| Number of pages | 10 |
| Journal | International Journal of Oncology |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Azoxymethane
- Colon cancer
- Cripto heterozygous mice
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
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.
In: International Journal of Oncology, Vol. 45, No. 1, 2014, p. 31-40.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cripto haploinsufficiency affects in vivo colon tumor development
AU - Giorgio, Emilia
AU - Liguoro, Annamaria
AU - D'Orsi, Luca
AU - Mancinelli, Sara
AU - Barbieri, Antonio
AU - Palma, Giuseppe
AU - Arra, Claudio
AU - Liguori, Giovanna L.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Azoxymethane
KW - Colon cancer
KW - Cripto heterozygous mice
UR - http://www.scopus.com/inward/record.url?scp=84902588983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902588983&partnerID=8YFLogxK
U2 - 10.3892/ijo.2014.2412
DO - 10.3892/ijo.2014.2412
M3 - Article
C2 - 24805056
AN - SCOPUS:84902588983
VL - 45
SP - 31
EP - 40
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 1
ER -