1. PKK deletion in basal keratinocytes promotes tumorigenesis after chemical carcinogenesis
- Author
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David Oleksyn, Elaine S. Gilmore, Kathleen Gillespie, Carolina V. Alexander-Savino, Matthew S. Hayden, Jiyong Zhao, Luojing Chen, and Brian Poligone
- Subjects
Keratinocytes ,0301 basic medicine ,Cancer Research ,Skin Neoplasms ,Carcinogenesis ,Pyridines ,9,10-Dimethyl-1,2-benzanthracene ,medicine.medical_treatment ,Protein Serine-Threonine Kinases ,medicine.disease_cause ,Targeted therapy ,Pathogenesis ,Mice ,03 medical and health sciences ,medicine ,Animals ,Humans ,Genes, Tumor Suppressor ,Basal cell carcinoma ,neoplasms ,Mice, Knockout ,Kinase ,business.industry ,Melanoma ,General Medicine ,medicine.disease ,stomatognathic diseases ,Cell Transformation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Knockout mouse ,Carcinogens ,Carcinoma, Squamous Cell ,Cancer research ,Keratinocyte ,business ,Signal Transduction - Abstract
Squamous cell carcinoma (SCC) of the skin is a keratinocyte malignancy characterized by tumors presenting on sun-exposed areas with surgery being the mainstay treatment. Despite advances in targeted therapy in other skin cancers, such as basal cell carcinoma and melanoma, there have been no such advances in the treatment of SCC. This is partly due to an incomplete knowledge of the pathogenesis of SCC. We have recently identified a protein kinase C-associated kinase (PKK) as a potential tumor suppressor in SCC. We now describe a novel conditional PKK knockout mouse model, which demonstrates that PKK deficiency promotes SCC formation during chemically induced tumorigenesis. Our results further support that PKK functions as a tumor suppressor in skin keratinocytes and is important in the pathogenesis of SCC of the skin. We further define the interactions of keratinocyte PKK with TP63 and NF-κB signaling, highlighting the importance of this protein as a tumor suppressor in SCC development.
- Published
- 2017
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