title: 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: Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China.
authors: Rongyi
authors: R
authors: Chen
authors: Meng
authors: M
authors: Fu
authors: Guoxue
authors: G
authors: Zhang
authors: Ying
authors: Y
authors: Zhou
authors: Shaojun
authors: S
authors: Zhu
authors: Juanjuan
authors: J
authors: Liu
authors: Dong
authors: D
authors: Wang
authors: Department of Laboratory Diagnostic, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Anmei
authors: A
authors: Deng
authors: 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, 710032, China.
authors: Zhipeng
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D053537:Keratin-17; D051379:Mice; D012307:Risk Factors; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D053537:Keratin-17; D020830:rac1 GTP-Binding Protein