Abstract
E-cadherin is a transmembrane protein that mediates Ca2+-dependent cell-cell adhesion and is implicated in a number of biologic processes, including cell growth and differentiation, cell recognition and cell sorting during development. We have previously demonstrated that both cell-cell adhesion and invasion are modulated by fibroblast growth factor (FGF)-1 and FGF-2 in a panel of pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF). Here, we examine further the role of FGFs in the expression and activation of the E-cadherin/catenin system. We demonstrate that both FGF-1 and FGF-2 upregulate E-cadherin and β-catenin at the protein level in the BxPc3 and HPAF cell lines and modestly in T3M4 cells. FGF-1 and FGF-2 facilitate the association of E-cadherin and α-catenin with the cytoskeleton, as demonstrated by the increase in the detergent-insoluble fraction of E-cadherin in BxPc3 and HPAF cells. Since the correct function of the E-cadherin/catenin complex requires its association with the cytoskeleton, our data suggest that FGF-1 and FGF-2 contribute to the integrity and thus the function of the complex. Furthermore, FGFs facilitate the assembly of the E-cadherin/catenin axis. The effect is associated with elevation of tyrosine phosphorylation of E-cadherin, α-catenin, β-4051 μcatenin and γ-catenin, but not p120ctn. These findings indicate that the E-cadherin/catenin system is a target of the FGF/FGFR system and that coordinated signals from both systems may determine the ultimate biologic responses.
| Original language | English |
|---|---|
| Pages (from-to) | 652-661 |
| Number of pages | 10 |
| Journal | International Journal of Cancer |
| Volume | 94 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Dec 1 2001 |
| Externally published | Yes |
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Keywords
- Catenins
- E-cadherin
- FGF
- FGFR
- Pancreatic adenocarcinoma
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma. / El-Hariry, Iman; Pignatelli, Massimo; Lemoine, Nicholas R.
In: International Journal of Cancer, Vol. 94, No. 5, 01.12.2001, p. 652-661.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma
AU - El-Hariry, Iman
AU - Pignatelli, Massimo
AU - Lemoine, Nicholas R.
PY - 2001/12/1
Y1 - 2001/12/1
N2 - E-cadherin is a transmembrane protein that mediates Ca2+-dependent cell-cell adhesion and is implicated in a number of biologic processes, including cell growth and differentiation, cell recognition and cell sorting during development. We have previously demonstrated that both cell-cell adhesion and invasion are modulated by fibroblast growth factor (FGF)-1 and FGF-2 in a panel of pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF). Here, we examine further the role of FGFs in the expression and activation of the E-cadherin/catenin system. We demonstrate that both FGF-1 and FGF-2 upregulate E-cadherin and β-catenin at the protein level in the BxPc3 and HPAF cell lines and modestly in T3M4 cells. FGF-1 and FGF-2 facilitate the association of E-cadherin and α-catenin with the cytoskeleton, as demonstrated by the increase in the detergent-insoluble fraction of E-cadherin in BxPc3 and HPAF cells. Since the correct function of the E-cadherin/catenin complex requires its association with the cytoskeleton, our data suggest that FGF-1 and FGF-2 contribute to the integrity and thus the function of the complex. Furthermore, FGFs facilitate the assembly of the E-cadherin/catenin axis. The effect is associated with elevation of tyrosine phosphorylation of E-cadherin, α-catenin, β-4051 μcatenin and γ-catenin, but not p120ctn. These findings indicate that the E-cadherin/catenin system is a target of the FGF/FGFR system and that coordinated signals from both systems may determine the ultimate biologic responses.
AB - E-cadherin is a transmembrane protein that mediates Ca2+-dependent cell-cell adhesion and is implicated in a number of biologic processes, including cell growth and differentiation, cell recognition and cell sorting during development. We have previously demonstrated that both cell-cell adhesion and invasion are modulated by fibroblast growth factor (FGF)-1 and FGF-2 in a panel of pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF). Here, we examine further the role of FGFs in the expression and activation of the E-cadherin/catenin system. We demonstrate that both FGF-1 and FGF-2 upregulate E-cadherin and β-catenin at the protein level in the BxPc3 and HPAF cell lines and modestly in T3M4 cells. FGF-1 and FGF-2 facilitate the association of E-cadherin and α-catenin with the cytoskeleton, as demonstrated by the increase in the detergent-insoluble fraction of E-cadherin in BxPc3 and HPAF cells. Since the correct function of the E-cadherin/catenin complex requires its association with the cytoskeleton, our data suggest that FGF-1 and FGF-2 contribute to the integrity and thus the function of the complex. Furthermore, FGFs facilitate the assembly of the E-cadherin/catenin axis. The effect is associated with elevation of tyrosine phosphorylation of E-cadherin, α-catenin, β-4051 μcatenin and γ-catenin, but not p120ctn. These findings indicate that the E-cadherin/catenin system is a target of the FGF/FGFR system and that coordinated signals from both systems may determine the ultimate biologic responses.
KW - Catenins
KW - E-cadherin
KW - FGF
KW - FGFR
KW - Pancreatic adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=0035545834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035545834&partnerID=8YFLogxK
U2 - 10.1002/ijc.1515
DO - 10.1002/ijc.1515
M3 - Article
VL - 94
SP - 652
EP - 661
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -