PROX1 Gene Editing    

The human PROX1 gene (prospero homebox gene 1) encodes a nuclear transcription factor that controls the differentiation of the lymphatic endothelium and is expressed in the nuclei of committed endothelial cells through a lymphatic lineage. Besides, PROX1 is involved in the development of liver, myocardial and pancreatic tissues. So far, the expression of PROX1 has been intensely studied not only in lymphatic vessels, but also in various tumors, such as breast cancer, pancreatic cancer, colon cancer, and ovarian cancer, as well as in vascular tumors, like the Kaposi sarcoma and the kaposiform hemangioendothelioma. The role of PROX1 in cancer is context and tumor type-dependent, because it has been shown to have both oncogenic and tumor-suppressive properties.

PROX1 in tumor progression

PROX1 protein is highly expressed in high-grade gliomas but is up-regulated also in a subset of diffuse low-grade gliomas with worse prognosis and likely to progress more rapidly to high-grade tumors. Therefore, while the experimental evidence that PROX1 actually leads to or sustains the progression to anaplastic tumor cells is still lacking, it has been shown that low-grade gliomas with a high proportion of PROX1 immunoreactive cells represent a more advanced, less differentiated phenotype than their counterparts with low PROX1 protein expression.

In colorectal cancer, PROX1 seems to promote progression from a benign to a malignant phenotype. Analysis of the PROX1 regulatory pathways showed that this phenotypic switch is most likely induced by alterations in cell polarity, extracellular matrix interactions and cell adhesion, and is associated with dysplasia and frequent mitotic figures. In addition, a study of Kaposiform hemangioendothelioma, known to highly resemble Kaposi sarcoma, showed that over-expression of PROX1 facilitates a more aggressive phenotype by inducing genes involved in cell adhesion, proteolysis and migration, thereby enhancing cell invasion and migration into the surrounding tissue.

PROX1 in tumor metastasis

Spread of tumor cells through lymphatic vessels from the primary bulk of the tumor to a distant organ is a common route of metastasis. Therefore, the degree of tumor lymphatic vascularization may influence the rate at which tumor cells disseminate. As a consequence, blocking lymphatic growth is considered to be a means to prevent metastatic tumor growth. PROX1’s contribution to cancer cell metastasis presumably resides on its role as a master regulator of the lymphatic system. Overexpression of PROX1 in blood endothelial cells will transform these cells into lymphatic endothelial cells. In addition, in PROX1 knockout mice, cells that would normally become lymphatic endothelial cells instead become blood endothelial cells. Thus, inhibiting PROX1 function may slow down cancer metastasis and hence serve as a novel target for metastasis prevention.

PROX1 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 PROX1 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• PROX1 Gene Knockout: We offer PROX1 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.
• PROX1 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop PROX1 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of PROX1 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.

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