机构：[1]Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China[2]Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China[3]The Helmholtz Sino-German Research Laboratory for Cancer, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi’an, China[4]Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, China[5]Department of Laboratory Diagnostic, Changhai Hospital, Second Military Medical University, Shanghai, China
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.
基金：
National Natural Science Foundation of China (No. 81071689, 81102066),International Communication and Collaboration Foundation of Shaanxi Province (2013KW30-01). Natural science foundation of china Guangdong Province of China (S2011040003129), Medical Research Foundation of Guangdong Province of China (A2011441), Shanghai Municipal Commission for Science and Technology (11JC1410902).
第一作者机构：[1]Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China
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推荐引用方式(GB/T 7714)：
Chen Rongyi,Fu Meng,Zhang Guoxue,et al.Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells.[J].ONCOTARGET.2014,5(12):4406-4417.doi:10.18632/oncotarget.2030.
APA：
Chen Rongyi,Fu Meng,Zhang Guoxue,Zhou Ying,Zhu Shaojun...&Wang Zhipeng.(2014).Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells..ONCOTARGET,5,(12)
MLA：
Chen Rongyi,et al."Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells.".ONCOTARGET 5..12(2014):4406-4417
