Targeting TUBB3 Suppresses Anoikis Resistance and Bone Metastasis in Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Bone metastases are prevalent in advanced prostate cancer (PCa), significantly worsening patient prognosis.
• Anoikis resistance, the ability of cancer cells to survive detachment, is a critical factor in tumor metastasis.
• Targeting anoikis resistance presents a significant therapeutic opportunity to combat metastatic spread.

Purpose of the Study:

• To identify key genes regulating anoikis resistance in PCa and evaluate their therapeutic potential.
• To investigate the role of TUBB3 in PCa bone metastasis and anoikis resistance.
• To develop and assess a novel targeted delivery system for therapeutic intervention in bone metastatic PCa.

Main Methods:

• Development of an anoikis-related prognostic risk model for PCa.
• Analysis of TUBB3 expression in PCa cells and its correlation with anoikis resistance, invasion, migration, and epithelial-mesenchymal transition (EMT).
• Creation of bone-targeting lipid nanoparticles (BT-LNP) for siRNA delivery (siTUBB3) and in vivo evaluation in a PCa bone metastasis model.

Main Results:

• TUBB3 was identified as a key anoikis-related gene highly expressed in bone metastatic PCa, correlating with anoikis resistance.
• TUBB3 depletion reversed anoikis resistance, inhibited PCa cell invasion, migration, and EMT, and reduced αvβ3/FAK/Src axis activation.
• BT-LNP-mediated systemic delivery of siTUBB3 effectively attenuated PCa bone metastasis progression in vivo.

Conclusions:

• TUBB3 is a critical regulator of anoikis resistance and a viable therapeutic target for bone metastatic PCa.
• BT-LNP-mediated delivery of siTUBB3 represents a novel and effective therapeutic strategy for treating PCa bone metastasis.