| Title |
Fibroblast Growth Factor Receptor-Mediated Activation of AKT-β-Catenin-CBP Pathway Regulates Survival and Proliferation of Murine Hepatoblasts and Hepatic Tumor Initiating Stem Cells
|
|---|---|
| Published in |
PLOS ONE, November 2012
|
| DOI | 10.1371/journal.pone.0050401 |
| Pubmed ID | |
| Authors |
Nirmala Mavila, David James, Sarah Utley, Nguyen Cu, Orly Coblens, Katrina Mak, C. Bart Rountree, Michael Kahn, Kasper S. Wang |
| Abstract |
Fibroblast Growth Factor (FGF)-10 promotes the proliferation and survival of murine hepatoblasts during early stages of hepatogenesis through a Wnt-β-catenin dependent pathway. To determine the mechanism by which this occurs, we expanded primary culture of hepatoblasts enriched for progenitor markers CD133 and CD49f from embryonic day (E) 12.5 fetal liver and an established tumor initiating stem cell line from Mat1a(-/-) livers in media conditioned with recombinant (r) FGF10 or rFGF7. FGF Receptor (R) activation resulted in the downstream activation of MAPK, PI3K-AKT, and β-catenin pathways, as well as cellular proliferation. Additionally, increased levels of nuclear β-catenin phosphorylated at Serine-552 in cultured primary hepatoblasts, Mat1a(-/-) cells, and also in ex vivo embryonic liver explants indicate AKT-dependent activation of β-catenin downstream of FGFR activation; conversely, the addition of AKT inhibitor Ly294002 completely abrogated β-catenin activation. FGFR activation-induced cell proliferation and survival were also inhibited by the compound ICG-001, a small molecule inhibitor of β-catenin-CREB Binding Protein (CBP) in hepatoblasts, further indicating a CBP-dependent regulatory mechanism of β-catenin activity. |
Mendeley readers
The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 5% |
| Portugal | 1 | 2% |
| Unknown | 38 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 24% |
| Student > Master | 6 | 15% |
| Professor > Associate Professor | 5 | 12% |
| Student > Bachelor | 5 | 12% |
| Researcher | 4 | 10% |
| Other | 9 | 22% |
| Unknown | 2 | 5% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 20 | 49% |
| Biochemistry, Genetics and Molecular Biology | 10 | 24% |
| Medicine and Dentistry | 6 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Neuroscience | 1 | 2% |
| Other | 0 | 0% |
| Unknown | 3 | 7% |