Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) i...
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MDPI AG
2015-02-01
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| Series: | Biomedicines |
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| Online Access: | http://www.mdpi.com/2227-9059/3/1/124 |
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| author | Valentina Sala Simona Gallo Stefano Gatti Elisa Vigna Antonio Ponzetto Tiziana Crepaldi |
| author_facet | Valentina Sala Simona Gallo Stefano Gatti Elisa Vigna Antonio Ponzetto Tiziana Crepaldi |
| author_sort | Valentina Sala |
| collection | DOAJ |
| description | Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr–Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC), increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr–Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr–Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle. |
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| id | doaj.art-34e89a816686473a884578e3e5d6d3b0 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-12-17T07:33:01Z |
| publishDate | 2015-02-01 |
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| spelling | doaj.art-34e89a816686473a884578e3e5d6d3b02022-12-21T21:58:25ZengMDPI AGBiomedicines2227-90592015-02-013112413710.3390/biomedicines3010124biomedicines3010124Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated MyotubesValentina Sala0Simona Gallo1Stefano Gatti2Elisa Vigna3Antonio Ponzetto4Tiziana Crepaldi5Department of Oncology, University of Turin, Corso Massimo D'Azeglio 52, 10126 Turin, ItalyDepartment of Oncology, University of Turin, Corso Massimo D'Azeglio 52, 10126 Turin, ItalyDepartment of Oncology, University of Turin, Corso Massimo D'Azeglio 52, 10126 Turin, ItalyDepartment of Oncology, Candiolo Cancer Institute—Fondazione del Piemonte per l'Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Strada Provinciale 142, Km 3.95, 10060 Candiolo, ItalyDepartment of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, ItalyDepartment of Oncology, University of Turin, Corso Massimo D'Azeglio 52, 10126 Turin, ItalyActivation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr–Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC), increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr–Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr–Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle.http://www.mdpi.com/2227-9059/3/1/124HGFMet receptormyogenic stem cellsskeletal muscledifferentiationproteasomeErk1,2 MAPK |
| spellingShingle | Valentina Sala Simona Gallo Stefano Gatti Elisa Vigna Antonio Ponzetto Tiziana Crepaldi Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes Biomedicines HGF Met receptor myogenic stem cells skeletal muscle differentiation proteasome Erk1,2 MAPK |
| title | Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes |
| title_full | Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes |
| title_fullStr | Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes |
| title_full_unstemmed | Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes |
| title_short | Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes |
| title_sort | anti differentiation effect of oncogenic met receptor in terminally differentiated myotubes |
| topic | HGF Met receptor myogenic stem cells skeletal muscle differentiation proteasome Erk1,2 MAPK |
| url | http://www.mdpi.com/2227-9059/3/1/124 |
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