Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo.
Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them...
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2014
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oai:doaj.org-article:e80dfd956d864a9686b67e0a730c2c232021-11-18T08:25:24ZLack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo.1932-620310.1371/journal.pone.0093469https://doaj.org/article/e80dfd956d864a9686b67e0a730c2c232014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24691449/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them with wild-type (WT) mice in a diethylnitrosamine (DEN) model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/-) mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/-) mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 μg/g body weight DEN treatment, the liver of Matn2(-/-) mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3α/β and retinoblastoma protein (p-Rb), decrease in p21/CIP1 level, and increase in β-Catenin protein expression were detected in Matn2(-/-) livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/-) livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3β, play strategic roles.Alexandra FullárKornélia BaghyFerenc DeákBálint PéterfiaYvonne ZsákPéter TátraiZsuzsa SchaffJózsef DudásIbolya KissIlona KovalszkyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e93469 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Alexandra Fullár Kornélia Baghy Ferenc Deák Bálint Péterfia Yvonne Zsák Péter Tátrai Zsuzsa Schaff József Dudás Ibolya Kiss Ilona Kovalszky Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| description |
Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them with wild-type (WT) mice in a diethylnitrosamine (DEN) model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/-) mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/-) mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 μg/g body weight DEN treatment, the liver of Matn2(-/-) mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3α/β and retinoblastoma protein (p-Rb), decrease in p21/CIP1 level, and increase in β-Catenin protein expression were detected in Matn2(-/-) livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/-) livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3β, play strategic roles. |
| format |
article |
| author |
Alexandra Fullár Kornélia Baghy Ferenc Deák Bálint Péterfia Yvonne Zsák Péter Tátrai Zsuzsa Schaff József Dudás Ibolya Kiss Ilona Kovalszky |
| author_facet |
Alexandra Fullár Kornélia Baghy Ferenc Deák Bálint Péterfia Yvonne Zsák Péter Tátrai Zsuzsa Schaff József Dudás Ibolya Kiss Ilona Kovalszky |
| author_sort |
Alexandra Fullár |
| title |
Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| title_short |
Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| title_full |
Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| title_fullStr |
Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| title_full_unstemmed |
Lack of Matrilin-2 favors liver tumor development via Erk1/2 and GSK-3β pathways in vivo. |
| title_sort |
lack of matrilin-2 favors liver tumor development via erk1/2 and gsk-3β pathways in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/e80dfd956d864a9686b67e0a730c2c23 |
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