KIF26B promotes bladder cancer progression through activating the NF-κB signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• The kinesin superfamily is implicated in tumor progression.
• KIF26B was previously identified as a biomarker for bladder cancer.
• The precise mechanisms of KIF26B in bladder cancer progression require further elucidation.

Purpose of the Study:

• To investigate the role of KIF26B in bladder cancer progression.
• To elucidate the molecular mechanisms by which KIF26B influences bladder cancer.
• To explore potential therapeutic strategies targeting KIF26B.

Main Methods:

• Investigated KIF26B's effect on the NF-κB signaling pathway.
• Analyzed KIF26B-mediated nuclear localization of NF-κB subunit p65.
• Examined the role of TRIM21 and K63-linked ubiquitination in p65 nuclear translocation.
• Studied the impact of PKCε-mediated phosphorylation of KIF26B on its interaction with p65.
• Assessed the positive feedback loop between KIF26B and NF-κB.
• Evaluated the combined effects of radiation and KIF26B blockage therapy.

Main Results:

• KIF26B activates the NF-κB signaling pathway by promoting p65 nuclear localization.
• KIF26B recruits TRIM21 to facilitate K63-linked ubiquitination of p65, enabling nuclear entry.
• PKCε phosphorylates KIF26B at S592 in response to TNFα, enhancing KIF26B-p65 interaction.
• The activated NF-κB pathway upregulates transcription of kif26b and her2, establishing a positive feedback loop.
• Combined radiation and KIF26B blockage therapy demonstrated superior anti-tumor efficacy.

Conclusions:

• KIF26B promotes bladder cancer progression by activating the NF-κB signaling pathway through a specific mechanism involving TRIM21 and PKCε.
• A KIF26B/NF-κB positive feedback loop contributes to bladder cancer advancement.
• Targeting KIF26B, particularly in combination with radiation, represents a promising therapeutic strategy for bladder cancer.