title: KLF5 promotes breast cancer proliferation, migration and invasion in part by upregulating the transcription of TNFAIP2.
abstract: The Kruppel-like factor 5 (KLF5) transcription factor is highly expressed in high-grade and basal-like breast cancers. However, the mechanism by which KLF5 promotes cell migration and invasion is still not completely understood. In this study, we demonstrate that TNFAIP2, a tumor necrosis factor-α (TNFα)-induced gene, is a direct KLF5 target gene. The expression of TNFAIP2 is highly correlated with the expression of KLF5 in breast cancers. The manipulation of KLF5 expression positively alters TNFAIP2 expression levels. KLF5 directly binds to the TNFAIP2 gene promoter and activates its transcription. Functionally, KLF5 promotes cancer cell proliferation, migration and invasion in part through TNFAIP2. TNFAIP2 interacts with the two small GTPases Rac1 and Cdc42, thereby increasing their activities to change actin cytoskeleton and cell morphology. These findings collectively suggest that TNFAIP2 is a direct KLF5 target gene, and both KLF5 and TNFAIP2 promote breast cancer cell proliferation, migration and invasion through Rac1 and Cdc42.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|Department of Biology, Yuxi Normal University, Yuxi, China.|University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|University of the Chinese Academy of Sciences, Beijing, China.|Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: P
authors.initials: P
authors.lastname: Shi
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.|University of the Chinese Academy of Sciences, Beijing, China.|Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer Hospital, Kunming Medical University, Kunming, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Hospital, Kunming Medical University, Kunming, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine & Central Laboratory, Southern Medical University-Affiliated Fengxian Hospital, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: C
authors.initials: C
authors.lastname: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; C085839:TNFAIP2 protein, human; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein