Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis

Jayesh Deshmukh; Ruth Pofahl; Herbert Pfister; Ingo Haase

doi:10.18632/oncotarget.11069

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis

Jayesh Deshmukh _, Ruth Pofahl, Herbert Pfister and Ingo Haase

PDF | HTML | How to cite

Oncotarget. 2016; 7:57841-57850. https://doi.org/10.18632/oncotarget.11069

Metrics: PDF 1989 views | HTML 3210 views | ?

Abstract

Jayesh Deshmukh1, Ruth Pofahl1, Herbert Pfister2, Ingo Haase1

1Department of Dermatology, University of Cologne, Cologne, 50937, Germany

2Institute of Virology, University of Cologne, Cologne, 50935, Germany

Correspondence to:

Jayesh Deshmukh, email: [email protected]

Keywords: HPV-8, Rac1, skin cancer, SCC, UV (Ultraviolet) light

Received: April 01, 2016 Accepted: July 19, 2016 Published: August 05, 2016

ABSTRACT

Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin.

To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 11069

Publication Alerts

Research Papers:

Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis

Abstract