c-Jun NH 2 -Terminal Kinase Activation Is Essential for DRAM-Dependent Induction of Autophagy and Apoptosis in 2-Methoxyestradiol–Treated Ewing Sarcoma Cells - Archive ouverte HAL Access content directly
Journal Articles Cancer Research Year : 2009

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

(1) , (1) , (1) , (2, 3) , (2, 3) , (4) , (1) , (1)
1
2
3
4

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.
Embargoed file
Embargoed file
Ne sera jamais visible

Dates and versions

inserm-03653080 , version 1 (27-04-2022)

Identifiers

Cite

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, 2009, 69 (17), pp.6924-6931. ⟨10.1158/0008-5472.CAN-09-1270⟩. ⟨inserm-03653080⟩

Collections

INSERM CNRS
3 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More