Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells.

Abstract

Rac1 is a member of the Rho family of small GTPases that control cells proliferation, differentiation, migration, and inflammation. Rac1 is crucial in tumorigenesis and development. Keratin17 and CD11b+Gr1+ cells are considered to regulate skin inflmmation. Here we discuss the regulation of Rac1 on skin tumor formation and its relationship. In samples from human skin squamous cell carcinoma (SCC), Rac1 activity was higher in cancer tissues than in normal skin and activity correlated with keratin 17 overexpression. In a DMBA/TPA-induced mouse skin tumor model, inhibition of Rac1 activity and depletion of CD11b+Gr1+ cells resulted in significant tumor formation. TPA induced recruitment of CD11b+Gr1+ cells into dermis; however, Rac1 inhibitor abolished this recruitment. In vitro, Rac1 induced interferon (IFN) and interlukin (IL6) production in keratinocytes, repression of keratin 17 inhibited IFN and IL6 production induced by Rac1. Moreover, both inhibition of Rac1 activity and repression of keratin 17 restricted proliferation and induction of differentiation in keratinocytes. Coculture of CD11b+Gr1+ cells with keratinocytes activated Wnt pathway in keratinocytes, resulting in enhanced Rac1 activity, overexpression of keratin 17, and hyperproliferation of keratinocytes. Our results suggested that hyperactive Rac1 recruited and interacted with CD11b+Gr1+ cells, inducing keratin 17-regulated inflammation and promoting skin tumor formation.

• Authors: Rongyi Chen, Meng Fu, Guoxue Zhang, Ying Zhou, Shaojun Zhu, Juanjuan Liu, Dong Wang, Anmei Deng, Zhipeng Wang
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 12 Pg. 4406-17 (Jun 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 24962779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD11b Antigen
• Keratin-17
• rac1 GTP-Binding Protein

Topics

• Animals
• CD11b Antigen (immunology, metabolism)
• Cell Differentiation
• Cell Proliferation
• Humans
• Keratin-17
• Mice
• Risk Factors
• Transfection
• rac1 GTP-Binding Protein (metabolism)