Abstract
Polo-like kinases (Plks) are critical regulatory molecules during the cell cycle process. This family has five members: Plk1, 2, 3, 4, and 5. Plk4 has been identified as a master regulator of centriole replication, and its aberrant expression is closely associated with cancer development. In this review, we depict the DNA, mRNA, and protein structure of Plk4, and the regulation of Plk4 at a molecular level. Then we list the downstream targets of Plk4 and the hallmarks of cancer associated with these targets. The role of Plk4 in different cancers is also summarized. Finally, we review the inhibitors that target Plk4 in the hope of discovering effective anticancer drugs. From authors’ perspective, Plk4 might represent a valuable tumor biomarker and critical target for cancer diagnosis and therapy.
Highlights
Centrosomes are recognized as microtubule-organizing centers (MTOCs) during mitosis in most eukaryotic cells
The size of the tumor and number of tumor-initiating cells could be reduced after CFI400945 treatment, and the overall survival of xenograft models was increased [166]. These results suggest that Plk4 inhibitors may be potential drugs for pancreatic cancer
In SK-N-BE [2] NB cells, downregulation of Plk4 via shRNA suppressed epithelial‒mesenchymal transition (EMT) and promoted apoptosis through the PI3K/Akt signaling pathway [138, 181]. These results revealed that targeting Plk4 as a promising therapeutic regimen for pediatric embryonal tumors is suitable for further investigation
Summary
Centrosomes are recognized as microtubule-organizing centers (MTOCs) during mitosis in most eukaryotic cells. Liu et al showed that the cancer cell motility was regulated via the interaction between CEP85, STIL, and Plk, and that downregulation of either CEP85 or STIL led to a reduced level of Arp phosphorylation and actin cytoskeleton reorganization [135]. An xenograft mouse model generated from HCT116 colon cancer cells revealed that centrosome amplification (CA) together with tumor growth were both dramatically enhanced by CEP131 upregulation [122] This may reveal the important function of Plk in regulating GIN. Kawakami et al showed that levels of Plk were higher in LAC and LSCC than in adjacent normal lung tissues, and that CFI-400945 treatment led to polyploidy and apoptosis in murine and human lung cancer cells by triggering multipolar mitotic defects [207]. CFI-400945 was the first orally available potent Plk inhibitor and it binds to the ATP-binding pocket of Plk
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