MTNR1B loss promotes chordoma recurrence by abrogating melatonin-mediated β-catenin signaling repression

Area of Science:

• Oncology
• Molecular Biology
• Cancer Stem Cell Research

Background:

• Chordoma is a rare bone cancer with high recurrence rates.
• Cancer stem cells (CSCs) drive tumor recurrence, self-renewal, and treatment resistance.
• The role of CSCs in chordoma recurrence and underlying molecular mechanisms are not fully understood.

Purpose of the Study:

• To investigate the role of cancer stem cells (CSCs) in chordoma recurrence.
• To identify molecular pathways involved in chordoma recurrence.
• To explore the potential of MTNR1B as a prognostic biomarker and therapeutic target.

Main Methods:

• Comparative analysis of primary and recurrent chordoma tissues.
• Investigation of MTNR1B expression and its downstream signaling pathways.
• Assessment of CSC properties, chemoresistance, and tumor progression.
• Correlation of MTNR1B deletion with patient survival data.

Main Results:

• Recurrent chordoma tissues exhibit increased CSC-like properties compared to primary tumors.
• MTNR1B deletion and downregulation are observed in recurrent chordoma.
• MTNR1B activation by melatonin inhibits SRC kinase and suppresses beta-catenin signaling, reducing stemness.
• MTNR1B loss enhances CSC properties, chemoresistance, and progression by releasing beta-catenin signaling repression.
• MTNR1B deletion correlates with poorer patient survival.

Conclusions:

• A novel link between melatonin and beta-catenin signaling pathways is established in chordoma recurrence.
• MTNR1B plays a critical role in regulating CSC properties and chemoresistance in chordoma.
• MTNR1B is a potential prognostic biomarker and therapeutic target for chordoma.
• Targeting the MTNR1B/Gαi2/SRC/β-catenin axis may benefit chordoma patients.