Abstract
Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells.
| Original language | English |
|---|---|
| Pages (from-to) | 178-189 |
| Number of pages | 12 |
| Journal | Cellular Signalling |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2013 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
}
Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors. / Nagaoka, Tadahiro; Karasawa, Hideaki; Turbyville, Thomas; Rangel, Maria Cristina; Castro, Nadia P.; Gonzales, Monica; Baker, Alyson; Seno, Masaharu; Lockett, Stephen; Greer, Yoshimi E.; Rubin, Jeffrey S.; Salomon, David S.; Bianco, Caterina.
In: Cellular Signalling, Vol. 25, No. 1, 01.01.2013, p. 178-189.Research output: Contribution to journal › Article
TY - JOUR
T1 - Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors
AU - Nagaoka, Tadahiro
AU - Karasawa, Hideaki
AU - Turbyville, Thomas
AU - Rangel, Maria Cristina
AU - Castro, Nadia P.
AU - Gonzales, Monica
AU - Baker, Alyson
AU - Seno, Masaharu
AU - Lockett, Stephen
AU - Greer, Yoshimi E.
AU - Rubin, Jeffrey S.
AU - Salomon, David S.
AU - Bianco, Caterina
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells.
AB - Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells.
UR - http://www.scopus.com/inward/record.url?scp=84867584073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867584073&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2012.09.024
DO - 10.1016/j.cellsig.2012.09.024
M3 - Article
C2 - 23022962
AN - SCOPUS:84867584073
VL - 25
SP - 178
EP - 189
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 1
ER -