Skip to Main content Skip to Navigation
Journal articles

c-Jun NH 2 -Terminal Kinase Activation Is Essential for DRAM-Dependent Induction of Autophagy and Apoptosis in 2-Methoxyestradiol–Treated Ewing Sarcoma Cells

Abstract : Ewing sarcoma and osteosarcoma are two aggressive cancers that affect bones and soft tissues in children and adolescents. Despite multimodal therapy, patients with metastatic sarcoma have a poor prognosis, emphasizing a need for more effective treatment. We have shown previously that 2-methoxyestradiol (2-ME), an antitumoral compound, induces apoptosis in Ewing sarcoma cells through c-Jun NH(2)-terminal kinase (JNK) activation. In the present study, we provide evidence that 2-ME elicits macroautophagy, a process that participates in apoptotic responses, in a JNK-dependent manner, in Ewing sarcoma and osteosarcoma cells. We also found that the enhanced activation of JNK by 2-ME is partially regulated by p53, highlighting the relationship of JNK and autophagy to p53 signaling pathway. Furthermore, we showed that 2-ME up-regulates damage-regulated autophagy modulator (DRAM), a p53 target gene, in Ewing sarcoma cells through a mechanism that involves JNK activation. The silencing of DRAM expression reduced both apoptosis and autophagy triggered by 2-ME in Ewing sarcoma and osteosarcoma cells. Our results therefore identify JNK as a novel mediator of DRAM regulation. These findings suggest that 2-ME or other anticancer therapies that increase DRAM expression or function could be used to effectively treat sarcoma patients.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03653080
Contributor : Mojgan Djavaheri-Mergny Connect in order to contact the contributor
Submitted on : Wednesday, April 27, 2022 - 12:47:04 PM
Last modification on : Sunday, June 26, 2022 - 12:18:25 PM
Long-term archiving on: : Friday, July 29, 2022 - 9:17:14 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Séverine Lorin, Amélie Borges, Lisandra Ribeiro dos Santos, Sylvie Souquère, Gérard Pierron, et al.. c-Jun NH 2 -Terminal Kinase Activation Is Essential for DRAM-Dependent Induction of Autophagy and Apoptosis in 2-Methoxyestradiol–Treated Ewing Sarcoma Cells. Cancer Research, American Association for Cancer Research, 2009, 69 (17), pp.6924-6931. ⟨10.1158/0008-5472.CAN-09-1270⟩. ⟨inserm-03653080⟩

Share

Metrics

Record views

3