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Oncogene. 2016 Apr 21;35(16):2040-51. doi: 10.1038/onc.2015.263. Epub 2015 Jul 20.

KLF5 promotes breast cancer proliferation, migration and invasion in part by upregulating the transcription of TNFAIP2.

Jia L1,2,3, Zhou Z1, Liang H1, Wu J1,3,4, Shi P1, Li F1, Wang Z1, Wang C1,3,5, Chen W6, Zhang H1, Wang Y6, Liu R1, Feng J7, Chen C1.

Author information

1
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.
2
Department of Biology, Yuxi Normal University, Yuxi, China.
3
University of the Chinese Academy of Sciences, Beijing, China.
4
Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, China.
5
Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
6
Cancer Hospital, Kunming Medical University, Kunming, China.
7
Department of Laboratory Medicine & Central Laboratory, Southern Medical University-Affiliated Fengxian Hospital, Shanghai, China.

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.

PMID:
26189798
DOI:
10.1038/onc.2015.263
[Indexed for MEDLINE]

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