PLK1 Gene Editing    

Polo-like kinase 1 (PLK1) belongs to the polo subfamily of Ser/Thr protein kinases (Plks), which play key roles in a variety of cellular processes including cell cycle progression, differentiation, and survival. PLK1 is expressed in embryonic tissues during development and mainly in proliferative tissues in adults. In mammalian cells, five Plks (Plk1 to 5) that exhibit different tissue distributions and physiological functions have been reported to date. A large body of evidence shows that Plk1 is highly expressed in mitotically active cells and tissues, and that it plays key roles at multiple stages of M-phase, including mitotic entry, metaphase/anaphase transition, and cytokinesis. In line with the multitude of Plk1 functions, Plk1 is located in the centrosomes, kinetochores, and midzones/midbodies in a temporally and spatially regulated manner. Therefore, Plk1 interacts with diverse targets at discrete subcellular locations to promote proper M-phase progression.

Figure 1. The Structures of the Human Plk Family and Subcellular Localization of Polo-Like Kinase 1 (Plk1) In the Cell Cycle. (Lee K S, et al., 2015)

PLK1 and Human Cancer

Since PLK1 was found to be highly expressed in primary tumor tissues more than 20 years ago, its role as an oncogene has been identified by many studies. A large number of studies have revealed that PLK1 is overexpressed in cancers compared with normal controls in various types of human cancers such as glioma, thyroid carcinoma, melanoma, colorectal cancers, head and neck squamous cell carcinoma, esophageal carcinoma, breast cancer, ovarian carcinoma, and prostate cancer. Overexpression of Plk1 is thought to promote tumorigenesis by overriding cellular checkpoints and inducing genetic instability. Interestingly, while Plk1 inhibition results in mitotic arrest and apoptotic cell death in a variety of human cancer cells, the 80% reduction of Plk1 has no significant detrimental effect in primary human cells and various organs of adult Plk1 RNAi mice. Cancer cells are known to be addicted to oncogenes and many non-oncogenes, such as Plk1. Reversing oncogene addictions in cancer cells has been shown to induce apoptotic cell death. Thus, increased sensitivity of cancer cells to Plk1 interrogation may be due to their altered signaling pathways and biochemical steps in Plk1-addicted cancer cells.

PLK1 as Targeted Cancer Therapeutic

Another major area in PLK1 research is developing PLK1 small-molecule inhibitors as drug therapies in diseases such as cancer. Many studies have tested PLK1 inhibitors, including BI2536, as potential cancer therapeutics for advanced metastatic tumors, including neuroblastoma, lung cancer, prostate cancer, and non-Hodgkin's lymphoma to name a few. These studies show elevated levels of PLK1 expression in highly metastatic and advanced cancers, resulting in chromosome instability and aneuploidy, providing these cells an advantage to overgrow and invade tissues. By inhibiting PLK1 activity in these cells, it is speculated that the cells will suffer cell cycle arrest, leading to cell death and hindered tumor growth, so as to improve the survival rate. The inhibitor BI2536 impeded tumor growth in mouse xenograph models. The overall survival of the animals significantly increased compared with the control group, indicating PLK1 inhibitors would be promising cancer therapeutics in clinical trials.

PLK1 Gene Editing Services

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively PLK1 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• PLK1 Gene Knockout: We offer PLK1 gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• PLK1 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop PLK1 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of PLK1 knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

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