Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes

Biomedicines

Valentina Sala²  Simona Gallo²  Stefano Gatti²  Elisa Vigna¹  Antonio Ponzetto¹  Tiziana Crepaldi² 

[1] Department 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, Italy; E-Mail:;Department of Oncology, University of Turin, Corso Massimo D’Azeglio 52, 10126 Turin, Italy; E-Mails:

关键词: HGF;    Met receptor;    myogenic stem cells;    skeletal muscle;    differentiation;    proteasome;    Erk1;    2 MAPK;   

DOI  :  10.3390/biomedicines3010124

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.