Inhibition of KIF14 Suppresses Tumor Cell Growth and Promotes Apoptosis in Human Glioblastoma

Abstract

Background/Aims: The mitotic kinesin superfamily protein KIF14 is essential for cytokinesis and chromosome segregation, and increased KIF14 expression is related to a variety of human cancers. However, the role of KIF14 in the development and malignant progression of astrocytomas and the underlying mechanisms remain unclear. The present study examined the relation between KIF14 and the pathogenesis of malignant astrocytoma. Methods and Results: The role of KIF14 in astrocytoma development and progression was investigated by analyzing KIF14 expression using SYBR Green quantitative real-time RT-PCR, western blotting and immunohistochemistry in human astrocytoma and normal brain tissues. KIF14 expression was higher in astrocytoma samples, and was positively correlated with pathological grade and proliferative activity indicated by Ki-67 staining. SiRNA knockdown of KIF14 inhibited tumor growth in vitro and in vivo, attenuated anchorage-independent growth, and induced G2/M phase arrest, cytokinesis failure and apoptosis in glioblastoma cell lines in association with decreased AKT phosphorylation and activity. Conclusions: The upregulation of KIF14 in astrocytoma is associated with disease severity, and suppression of KIF14 inhibits cell proliferation and induces apoptosis through a mechanism involving the inactivation of AKT signaling, suggesting that KIF14 plays an important role in astrocytoma tumorigenesis and could be a promising molecular target for anticancer therapy.

Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

“…43 Kinesin family member 14 (KIF14) encodes a member of the kinesin-3 superfamily of microtubule motor proteins that acts to bundle and stabilize midbody microtubules during cytokinesis. 44 KIF14 acts as an oncogene in many cancer entities, including esophageal squamous cell carcinoma, 45 cervical and ovarian cancers, 46, 47 gliomas, 48 retinoblastoma, 49, 50 glioblastoma, 51 hepatocellular carcinoma, 52 lung adenocarcinoma, 53 laryngeal carcinoma, 54 synovial carcinomas 55 and papillary renal cell tumors. 56 KIF14 is present in the minimal region of chromosome 1q gain in breast cancer cell lines, is overexpressed in breast cancers and its expression positively correlates with tumor aggressiveness.…”

Valproic Acid Promotes Human Glioma U87 Cells Apoptosis and Inhibits Glycogen Synthase Kinase-3β Through ERK/Akt Signaling

“…The activation of the MAPK pathway by different stimuli may lead to GSK3β inhibition [58,59,63]. In addition, as the major target of the PI3K, Akt regulates many downstream targets for the execution of its cell functions (such as cell growth and migration) [64][65][66]. Previous studies showed that Akt activation led to GSK3β phosphorylation [67,68], while others showed that lithium was able to activate PI3K and Akt and in turn to induce GSK3β phosphorylation and inactivation [69,70].…”

Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis

“…This protein is encoded by the 15 exon-spanning MKI67 gene mapping to chromosome 10q26.2 [38,39]. Moreover, Ki-67 expression is strongly associated with the percentage of growth, and this index is used for measuring tumor cell proliferation [40,41].…”