PKN3 is the major regulator of angiogenesis and tumor metastasis in mice
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Updated: Mar 27, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Hideyuki Mukai1, Aiko Muramatsu2, Rana Mashud3
1Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
Abstract:
PKN, a conserved family member related to PKC, was the first protein kinase identified as a target of the small GTPase Rho. PKN is involved in various functions including cytoskeletal arrangement and cell adhesion. Furthermore, the enrichment of PKN3 mRNA in some cancer cell lines as well as its requirement in malignant prostate cell growth suggested its involvement in oncogenesis. Despite intensive research efforts, physiological as well as pathological roles of PKN3 in vivo remain elusive. Here, we generated mice with a targeted deletion of PKN3. The PKN3 knockout (KO) mice are viable and develop normally. However, the absence of PKN3 had an impact on angiogenesis as evidenced by marked suppressions of micro-vessel sprouting in ex vivo aortic ring assay and in vivo corneal pocket assay. Furthermore, the PKN3 KO mice exhibited an impaired lung metastasis of melanoma cells when administered from the tail vein. Importantly, PKN3 knock-down by small interfering RNA (siRNA) induced a glycosylation defect of cell-surface glycoproteins, including ICAM-1, integrin β1 and integrin α5 in HUVECs. Our data provide the first in vivo genetic demonstration that PKN3 plays critical roles in angiogenesis and tumor metastasis, and that defective maturation of cell surface glycoproteins might underlie these phenotypes.
Insights
Protein kinase N (PKN) plays a critical role in angiogenesis and cancer metastasis. PKN3 knockout mice show impaired blood vessel formation and reduced melanoma cell lung metastasis, suggesting a role in glycoprotein maturation.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Protein kinase N (PKN) is a conserved kinase family and a target of the small GTPase Rho.
- PKN is implicated in cytoskeletal arrangement, cell adhesion, and potentially oncogenesis due to PKN3 mRNA enrichment in cancer cells.
- The in vivo physiological and pathological roles of PKN3 have remained largely unknown.
Purpose of the Study:
- To investigate the in vivo function of PKN3.
- To determine the role of PKN3 in angiogenesis and tumor metastasis.
- To elucidate the molecular mechanisms underlying PKN3's function.
Main Methods:
- Generation of PKN3 knockout (KO) mice via targeted deletion.
- Assessment of angiogenesis using ex vivo aortic ring and in vivo corneal pocket assays.
- Evaluation of lung metastasis in PKN3 KO mice after melanoma cell administration.
- PKN3 knockdown using small interfering RNA (siRNA) in human umbilical vein endothelial cells (HUVECs).
Main Results:
- PKN3 KO mice were viable and developed normally but exhibited suppressed micro-vessel sprouting in angiogenesis assays.
- PKN3 KO mice showed impaired lung metastasis of melanoma cells.
- PKN3 knockdown in HUVECs led to glycosylation defects in cell-surface glycoproteins like ICAM-1 and integrins.
Conclusions:
- This study provides the first in vivo genetic evidence for PKN3's critical roles in angiogenesis and tumor metastasis.
- Defective maturation of cell surface glycoproteins is a potential mechanism underlying PKN3's function in these processes.
- PKN3 is a significant factor in regulating blood vessel formation and cancer cell dissemination.
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