PKK deletion in basal keratinocytes promotes tumorigenesis after chemical carcinogenesis

Department

Research

Document Type

Article

Publication Title

Carcinogenesis

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.

First Page

418

Last Page

428

DOI

10.1093/carcin/bgx120

Volume

39

Issue

3

Publication Date

3-8-2018

Medical Subject Headings

9,10-Dimethyl-1,2-benzanthracene (toxicity); Animals; Carcinogens (toxicity); Carcinoma, Squamous Cell (chemically induced, genetics, pathology); Cell Transformation, Neoplastic (genetics); Genes, Tumor Suppressor; Humans; Keratinocytes (drug effects, pathology); Mice; Mice, Knockout; Protein Serine-Threonine Kinases (genetics); Pyridines (toxicity); Signal Transduction (physiology); Skin Neoplasms (chemically induced, genetics, pathology)

PubMed ID

29186361

Link to Full Text

Share

COinS