Disease relevance of KIF14

• KIF14 protein was overexpressed in retinoblastoma tumors and breast cancer cell lines by immunoblot [1].
• KIF14 mRNA was expressed in 20/22 retinoblastoma samples 100-1000-fold higher than in retina (t-test P=0.00002); cell lines (n=10) had higher levels than tumors (n=12) (P=0.009) [1].
• KIF14 was expressed in 4/4 breast cancer cell lines 31-92-fold higher than in normal breast tissue, in 5/5 medulloblastoma cell lines 22-79-fold higher than in fetal brain, and in 10/22 primary lung tumors 3-34-fold higher than in normal lung [1].
• KIF14 expression is independently prognostic for disease-free survival in lung cancer and knockdown decreases tumorigenicity in vitro, showing that it is a clinically relevant oncogene and an exciting therapeutic target for further study [2].

High impact information on KIF14

• We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis [3].
• KIF14 and citron kinase act together to promote efficient cytokinesis [3].
• KIF14 is a microtubule motor protein whose elevated expression is associated with poor-prognosis breast cancer [4].
• Here we demonstrate KIF14 accumulation in mitotic cells, where it associated with developing spindle poles and spindle microtubules [4].
• RNA Interference-Mediated Silencing of Mitotic Kinesin KIF14 Disrupts Cell Cycle Progression and Induces Cytokinesis Failure [4].

Biological context of KIF14

• KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers [1].
• Cells at later stages of mitosis were characterized by the concentration of KIF14 at the midbody [4].
• Furthermore, the link we observed between siRNA efficacy and phenotypic outcome indicates that distinct stages during cell cycle progression are disrupted by the differential modulation of KIF14 expression [4].
• Time-lapse microscopy revealed that strong RNA interference (RNAi)-mediated silencing of KIF14 induced cytokinesis failure, causing several rounds of endoreduplication and resulting in multinucleated cells [4].
• Additionally, less efficacious KIF14-specific short interfering RNAs (siRNAs) induced multiple phenotypes, all of which resulted in acute apoptosis [4].

Anatomical context of KIF14

• KIF14 expression correlated positively with Ki-67 mRNA level (Spearman r = 0.692, p = 0.000001), fraction of positive nodes (r = 0.227, p = 0.024) and percent invasive cells (r = 0.360, p = 0.0002), and negatively with percent fatty stroma (r = -0.258, p = 0.010) and percent normal epithelium (r = -0.291, p = 0.003) [5].

Other interactions of KIF14

• Of these, only KIF14, a putative chromokinesin, was overexpressed in various cancers by real-time RT-PCR [1].
• Measured by real-time RT-PCR, KIF14 was overexpressed 10-fold on average in tumors relative to normals (t test p = 0.000054); expression increased with grade (ANOVA p = 0.000006) [5].

Analytical, diagnostic and therapeutic context of KIF14

• KIF14 overexpression also predicted decreased disease-free survival (log-rank p = 0.049) [5].
• Novel high-level amplification of 1q32.1 in one primary tumor, confirmed by fluorescence in situ hybridization, strongly supports the presence of oncogene(s) in this region, possibly the mitotic kinesin, KIF14 [6].

References