Kif14 overexpression accelerates murine retinoblastoma development

Area of Science:

• Cell Biology
• Molecular Oncology
• Cancer Genetics

Background:

• The mitotic kinesin KIF14 is crucial for cytokinesis and is overexpressed in various cancers, suggesting oncogenic activity.
• Previous studies indicated KIF14's oncogenic properties in vitro and in xenografts, but its role in vivo tumor progression remained uninvestigated.
• Retinoblastoma is a pediatric eye cancer associated with genomic alterations in KIF14.

Purpose of the Study:

• To investigate the role of KIF14 in promoting retinal tumor formation using a novel transgenic mouse model.
• To determine if KIF14 overexpression accelerates tumor initiation and progression in vivo.

Main Methods:

• Developed a novel double transgenic mouse model overexpressing KIF14 and simian virus 40 large T-antigen (TAg) for retinoblastoma (RB).
• Monitored tumor initiation and development in vivo over time using optical coherence tomography (OCT).
• Quantified ex vivo tumor burden and calculated tumor doubling times.

Main Results:

• KIF14 overexpression significantly accelerated tumor initiation in the TAg-RB mouse model.
• Tumor doubling time was reduced in KIF14-overexpressing mice (1.8 weeks) compared to controls (2.9 weeks).
• Overall tumor burden was significantly increased by KIF14 overexpression.

Conclusions:

• KIF14 acts as an oncogene by promoting tumor formation in susceptible cells in vivo.
• These findings provide the first in vivo evidence of KIF14's role in promoting tumor progression.
• KIF14 may be a potential therapeutic target for retinoblastoma and other cancers with KIF14 alterations.