DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Osteosarcoma (OS) is a primary bone cancer with poor prognosis due to treatment resistance and recurrence.
• DJ-1 (PARK7) is an oncogene implicated in various cancers, correlating with poor patient outcomes.

Purpose of the Study:

• To investigate the role of DJ-1 in osteosarcoma progression and its underlying molecular mechanisms.
• To explore DJ-1 as a potential therapeutic target for osteosarcoma.

Main Methods:

• In vitro studies assessed DJ-1's effect on OS cell proliferation, migration, and chemotherapy resistance.
• Investigated DJ-1's interaction with CDK4, AKT pathway, and its role in RB phosphorylation and E2F1 nuclear translocation.
• Utilized a tumor xenograft mouse model to evaluate DJ-1's in vivo impact on tumor growth.

Main Results:

• Upregulated DJ-1 expression correlated with poor prognosis in OS patients.
• DJ-1 promoted OS cell proliferation, migration, and chemoresistance by regulating CDK4 activity, not via oxidation or AKT.
• DJ-1 and CDK4 co-regulation led to RB phosphorylation, E2F1 nuclear translocation, and cell cycle gene expression.
• DJ-1 knockout significantly suppressed tumor growth in vivo.

Conclusions:

• DJ-1 influences osteosarcoma occurrence and progression through the CDK/RB/E2F1 axis.
• Targeting DJ-1 presents a novel therapeutic avenue for osteosarcoma patients.