Kif14: A Clinically Relevant Kinesin and Potential Target for Cancer Therapy

Thériault, Brigitte L.; Corson, Timothy W.

doi:10.1007/978-94-017-9732-0_10

Cited by 6 publications

(13 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show that the overexpression of Kif14 accelerates tumor onset and increases tumor burden and tumor proliferation rate in the TAg‐RB retinoblastoma model. This provides strong evidence that KIF14 is indeed an oncogene, when considered in concert with previous clinical, in vitro and xenograft findings …”

Section: Discussionsupporting

confidence: 78%

“…Increased proliferation of Kif14 overexpressing tumor cells is consistent with previous in vitro work. Overexpression of KIF14 in hepatocellular carcinoma, lung and ovarian cancer cell lines markedly increased their proliferation capacity, and a similar effect was seen in immortalized mammary epithelial cells . It will be interesting to assess if Kif14 loss in the context of TAg‐RB would slow tumor growth, as it does in cell and xenograft models.…”

Section: Discussionmentioning

confidence: 85%

“…In TAg‐RB, the Kif14 ‐overexpressing tumor cells likely have increased resistance to apoptosis; a wave of apoptosis normally kills off the majority of TAg‐positive cells in TAg‐RB eyes around Week 4, while many cells remain when Kif14 is overexpressed. Increased apoptosis is a hallmark of Kif14 loss in mice or knockdown in cancer cells in vitro , so the converse could also be true: Kif14 overexpression may block apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…However KIF14 also has cytokinesis independent roles, including negative regulation of Rap1a‐Radil signaling at the cell membrane . Although the exact molecular functions of KIF14 are still under investigation, a large body of evidence implicates it as an oncogene . It is gained at the DNA level in tumors such as hepatocellular, renal and ovarian carcinoma .…”

mentioning

confidence: 99%

“…Moreover, in these cancers KIF14 levels are prognostic for outcome. KIF14 knockdown decreases tumorigenicity in vitro and in xenografts, while overexpression enhances growth …”

mentioning

confidence: 99%

See 4 more Smart Citations

Kif14 overexpression accelerates murine retinoblastoma development

O’Hare

Shadmand

Sulaiman

et al. 2016

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Moreover, in these cancers KIF14 levels are prognostic for outcome. KIF14 knockdown decreases tumorigenicity in vitro and in xenografts, while overexpression enhances growth …”

mentioning

confidence: 99%

See 3 more Smart Citations

Kif14 overexpression accelerates murine retinoblastoma development

O’Hare

Shadmand

Sulaiman

et al. 2016

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

Sishtla

Pitt

Shadmand

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

The KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, liver, ovarian, breast, prostate, and other tumour cells and xenografts. However, the tumour-initiating effects of Kif14 overexpression have not been studied. We aged a cohort of Kif14-overexpressing transgenic mice and wild-type littermates and documented survival, cause of death, and tumour burden. The Kif14 transgene was expressed in all tissues examined, and was associated with increased proliferation marker expression. Neither mouse weights nor overall survival differed between genotypes. However, Kif14 transgenic mice showed a higher incidence of fatal lymphomas (73 vs. 50%, p = 0.03, Fisher’s exact test), primarily follicular and diffuse B-cell lymphomas. Non-tumour findings included a bilateral ballooning degeneration of lens in 12% of Kif14 transgenic mice but no wild-type mice (p = 0.02). Overall, this work reveals a novel association of Kif14 overexpression with lymphoma but suggests that Kif14 does not have as prominent a role in initiating cancer in other cell types as it does in accelerating tumour development in response to other oncogenic insults.

show abstract

Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data

Wang

2017

Medicine

View full text Add to dashboard Cite

Background:To identify gastric cancer (GC)-associated genes and transcription factors (TFs) using RNA-sequencing (RNA-seq) data of Asians.Materials and methods:The RNA-seq data (GSE36968) were downloaded from Gene Expression Omnibus database, including 6 noncancerous gastric tissue samples, 5 stage I GC samples, 5 stage II GC samples, 8 stage III GC samples, and 6 stage IV GC samples. The gene expression values in each sample were calculated using Cuffdiff. Following, stage-specific genes were identified by 1-way analysis of variance and hierarchical clustering analysis. Upstream TFs were identified using Seqpos. Besides, functional enrichment analysis of stage-specific genes was performed by DAVID. In addition, the underlying protein–protein interactions (PPIs) information among stage IV-specific genes were extracted from STRING database and PPI network was constructed using Cytoscape software.Results:A total of 3576 stage-specific genes were identified, including 813 specifically up-regulated genes in the normal gastric tissues, 2224 stage I and II-specific genes, and 539 stage IV-specific genes. Also, a total of 9 and 11 up-regulated TFs were identified for the stage I and II-specific genes and stage IV-specific genes, respectively. Functional enrichment showed SPARC, MMP17, and COL6A3 were related to extracellular matrix. Notably, 2 regulatory pathways HOXA4-GLI3-RUNX2-FGF2 and HMGA2-PRKCA were obtained from the PPI network for stage IV-specific genes. In the PPI network, TFs HOXA4 and HMGA2 might function via mediating other genes.Conclusion:These stage-specific genes and TFs might act in the pathogenesis of GC in Asians.

show abstract

Kif14: A Clinically Relevant Kinesin and Potential Target for Cancer Therapy

Cited by 6 publications

References 66 publications

Kif14 overexpression accelerates murine retinoblastoma development

Kif14 overexpression accelerates murine retinoblastoma development

Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data

Contact Info

Product

Resources

About