Sanna, Luca and Piredda, Roberta and Marchesi, Irene and Bordoni, Valentina and Forcales, Sonia Vanina and Calvisi, Diego Francesco and Bagella, Luigi (2019) Verteporfin exhibits anti-proliferative activity in embryonal and alveolar rhabdomyosarcoma cell lines. CHEMICO-BIOLOGICAL INTERACTIONS, 312: 108813. ISSN 0009-2797, 1872-7786
Full text not available from this repository. (Request a copy)Abstract
Rhabdomyosarcoma (RMS) is a pediatric tumor, which arises from muscle precursor cells. Recently, it has been demonstrated that Hippo Pathway (Hpo), a pathway that regulates several physiological and biological features, is involved in RMS tumorigenesis. For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells. On the other hand, the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ) is overexpressed in alveolar rhabdomyosarcoma (aRMS) patients with poor survival. YAP and TAZ exhibit both cytoplasmic and nuclear functions. In the nucleus, YAP binds TEADs (TEA domain family members) factors and together they constitute a complex that is able either to activate the transcription of several genes such as MYC, Tbx5 and PAX8 or to maintain the stability of others like p73. Due to the key role of YAP and TAZ in cancer, the identification and/or development of new compounds able to block their activity might be an effective antineoplastic strategy. Verteporfin (VP) is a molecule able to stop the formation of YAP/TEAD complex in the nucleus. The aim of this study is to evaluate the action of VP on RMS cell lines. This work shows that VP has an anti-proliferative activity on all RMS cell lines analyzed. Depending on RMS cell lines, VP affects cell cycle differently. Moreover, VP is able to decrease YAP protein levels, and to induce the activation of apoptosis mechanism through the cleavage of PARP-1. In addition, Annexin V assay showed the activation of apoptosis and necrosis after VP treatment. In summary, the ability of VP to disrupt RMS cell proliferation could be a novel and valuable strategy to improve the therapeutic approaches in treating rhabdomyosarcoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIPPO PATHWAY; STRUCTURAL-ANALYSIS; TAZ; YAP; PROLIFERATION; APOPTOSIS; GROWTH; INHIBITION; PROMOTES; PROTEIN; Rhabdomyosarcoma; Verteporfin; YAP; TAZ; Cancer; Anti-proliferation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2020 05:52 |
| Last Modified: | 27 Mar 2020 05:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26167 |
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