Format

Send to

Choose Destination
J Invest Dermatol. 2015 Mar;135(3):869-876. doi: 10.1038/jid.2014.428. Epub 2014 Oct 6.

PKK suppresses tumor growth and is decreased in squamous cell carcinoma of the skin.

Author information

1
Department of Dermatology, University of Rochester School of Medicine, Rochester, New York, USA; James P Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA. Electronic address: brian_poligone@urmc.rochester.edu.
2
Department of Dermatology, University of Rochester School of Medicine, Rochester, New York, USA; James P Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
3
Department of Dermatology, University of Rochester School of Medicine, Rochester, New York, USA.
4
Department of Biomedical Genetics, University of Rochester School of Medicine, Rochester, New York, USA.

Abstract

Non-melanoma skin cancer represents the most common cancer in the United States. Squamous cell carcinoma (SCC) of the skin is a subtype of NMSC that shows a greater potential for invasion and metastasis. The current study identifies the protein kinase C-associated kinase (PKK), which is also known as the receptor-interacting protein kinase 4, as a suppressor of tumor growth in SCC of the skin. We show that expression of PKK is decreased in human SCC of the skin compared with normal skin. Further, suppression of PKK in human keratinocytes leads to increased cell proliferation. The use of RNA interference to reduce PKK expression in keratinocytes leads to an increase in S phase and in proteins that promote cell cycle progression. Consistent with the results obtained from cell culture, there is a marked increased tumorigenesis after PKK knockdown in a xenotransplant model and in soft agar assays. The loss of tumor suppression involves the NF-κB and p63 pathways. NF-κB is inhibited through inhibition of inhibitor of NF-κB kinase function and there is increased nuclear TP63 activity after PKK knockdown. This study opens new avenues both in the discovery of disease pathogenesis and for potential treatments.

PMID:
25285922
PMCID:
PMC4324088
DOI:
10.1038/jid.2014.428
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center