Kif14 overexpression accelerates murine retinoblastoma development

Abstract

The mitotic kinesin KIF14 has an essential role in the recruitment of proteins required for the final stages of cytokinesis. Genomic gain and/or overexpression of KIF14 has been documented in retinoblastoma and a number of other cancers, such as breast, lung and ovarian carcinomas, strongly suggesting its role as an oncogene. Despite evidence of oncogenic properties in vitro and in xenografts, Kif14’s role in tumor progression has not previously been studied in a transgenic cancer model. Using a novel Kif14 overexpressing, simian virus 40 large T-antigen retinoblastoma (TAg-RB) double transgenic mouse model, we aimed to determine Kif14’s role in promoting retinal tumor formation. Tumor initiation and development in double transgenics and control TAg-RB littermates were documented in vivo over a time-course by optical coherence tomography, with subsequent ex vivo quantification of tumor burden. Kif14 overexpression led to an accelerated initiation of tumor formation in the TAg-RB model and a significantly decreased tumor doubling time (1.8 vs. 2.9 weeks). Moreover, overall percentage tumor burden was also increased by Kif14 overexpression. These data provide the first evidence that Kif14 can promote tumor formation in susceptible cells in vivo.

The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

“…7,14 In vivo model also demonstrated upregulation of KIF14 resulted in increased tumor growth rate and accelerated tumor initiation. 12 This study demonstrated the increased mRNA abundance of KIF14 in MB. This finding was also in line with previous study showing a profound upregulation of KIF14 in MB compared with fetal brain.…”

“…10,11 It has been shown that KIF14 overexpression accelerated initiation of tumor formation. 12 In contrast, siRNA-induced silencing KIF14 resulted in tumor growth inhibition and cell cycle arrest in hepatocellular carcinoma and glioma. 13,14 In the present study, we demonstrated increased KIF14 mRNA and protein abundance in MB samples.…”

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

“…Retinoblastoma was among the first tumors where KIF14 overexpression was noted [56] , and KIF14 overexpression was found to accelerate retinoblastoma tumorigenesis in a murine model [57] . KIF14 overexpression has also been found in both ovarian and chemo-resistant breast cancers, where KIF14 inhibition leads to chemo-sensitization [58, 59] .…”

Retinoblastoma, the visible CNS tumor: A review

“…More recently, using a commercially available small‐animal OCT system, we showed that this technique can detect the earliest signs of tumors in the TAg‐RB model, corresponding to their first appearance by histology (Figure g) (Wenzel, O’Hare, Shadmand, & Corson, ), and we used this finding to show that overexpression of the oncogene Kif14 accelerates not just tumor growth but also tumor initiation in this model (O’Hare et al, ).…”