PTK7 Gene Editing    

Protein tyrosine kinase 7 (PTK7) belongs to the receptor protein tyrosine kinase-like family. PTK7 is a cyto-membrane protein highly expressed in CCRF-CEM cells. PTK7 has been shown to be highly involved in both canonical and noncanonical Wnt pathways. It plays a role in a variety of cellular processes including tube formation, migration, and invasion of endothelial cells and angiogenesis. PTK7 may affect cell clustering or cell contact persistence. Notably, the potential role of PTK7 in the progression of a variety of cancers has been widely revealed. PTK7 was highly expressed in several cancers, such as lung cancer, gastric cancer, and colon cancer. In liposarcoma, PTK7 affects cell proliferation and invasion. PTK7 also contributes to cancer stemness of head and neck cancer.

PTK7 and Wnt Signaling Pathways

Despite the lack of catalytic activity, PTK7 seems to have a role in signal transduction and emerges as an important regulator of VEGFR1 and Wnt pathways. In endothelial cells, VEGFA triggers VEGFR1 phosphorylation and association with PTK7. This interaction is necessary for optimal phosphorylation and activation of downstream components of VEGFR1 signaling, including AKT and FAK required for the angiogenic process. Therefore, downregulation of PTK7 expression in vitro and in vivo results in a decreased angiogenesis. Interestingly, an anti-angiogenic effect can also be obtained using a soluble recombinant form of PTK7, indicating a dominant-negative effect on the extracellular domain and the capture of a putative ligand.

Figure 1. Role of PTK7 in non-canonical Wnt pathway or PCP. (Lhoumeau A C, et al. 2015)

Wnt pathways are divided into canonical (β-catenin dependent) and noncanonical (β-catenin independent) pathways. While canonical Wnts such as Wnt3a stabilize β-catenin and promote its transcriptional functions, non-canonical Wnts (Wnt5a, Wnt11) use Fz receptors and PCP proteins, including PTK7, to promote the so-called PCP pathway inducing a Rho/Rac/JNK signaling cascade that controls actin cytoskeleton remodeling. Through a mouse gene trap-screen for transmembrane proteins with a function in neural development, PTK7 mutants were identified showing a combination of serious neural tube closure and inner ear polarity defects. Based on this mutant phenotype, which is typical for known regulators of PCP, and its genetic interaction with Vangl2, PTK7 was added to the list of vertebrate PCP regulators. Further functional studies using mouse, zebrafish and Xenopus confirmed the function of PTK7 in the process of PCP signal regulation, including convergent extension movements during gastrulation, neurulation and Wolffian duct elongation, as well as neural crest migration and wound healing.

PTK7 and Disease

In humans, a deregulated expression of PTK7 mRNA has been documented at the transcriptomic level in solid tumors including pulmonary adenocarcinoma, colon cancers, gastric cancers, and metastatic melanoma, breast cancer, prostate cancer, intrahepatic cholangiocarcinoma, esophageal squamous cell carcinoma, and glioma cells. PTK7 is overexpressed in all these cancers, except in advanced stage melanoma, where it is downregulated as compared with localized tumors. In advanced lung squamous cell carcinoma, PTK7 is also downregulated and appears to play a tumor suppressing role by inhibiting ERK and AKT activity. Although the mechanistic contribution of PTK7 to the respective tumor phenotypes is unclear, the upregulation of PTK7 in many tumor types makes it an attractive tumor marker and therapeutic target. In fact, the first PTK7 specific reagents with potential clinical applications have been published, including a PTK7-specific fluorescently labeled aptamer for in vivo detection of tumor tissue. Interestingly, PTK7 has recently been established as a marker for normal colon stem cells and as a marker for tumor initiating cells in triple-negative breast cancer, non-small cell lung cancer and ovarian cancer. The authors of the latter study also developed a PTK7-targeted antibody-drug conjugate and showed that its application can reduce tumor initiating cells and induce sustained tumor regressions, paving the way for a PTK7-directed anti-tumor therapy.

PTK7 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 PTK7 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• PTK7 Gene Knockout: We offer PTK7 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.
• PTK7 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop PTK7 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of PTK7 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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