Krüppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E2 Synthase 1 Gene Transcription in Breast Cancer

Xia, Houjun; Wang, Chunyan; Chen, Wenlin; Zhang, Hailin; Chaudhury, L; Zhou, Zhongmei; Liu, Rong; Chen, Ceshi

doi:10.1074/jbc.m113.483958

Cited by 43 publications

(52 citation statements)

References 56 publications

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“…In addition, flagellinand poly(I:C)-induced IL6 and IL8 mRNA expression was also significantly reduced in KLF5 knockout cells. Concurrent with these findings, knockdown of KLF5 by siRNA inhibits TNFa-induced MCP1 expression in endothelial cells (Kumekawa et al 2008), LPS-induced TNFa and IL6 in intestinal epithelial cells (Chanchevalap et al 2006); and microsomal PGE 2 synthase 1 (mPGES1) mRNA and protein expression and subsequent PGE 2 synthesis in breast cancer cells (Xia et al 2013). In vivo, epithelial COX2 expression is absent with loss of KLF5 (Sun et al 2012); KLF5 heterozygous knockout mice show an attenuated induction of hyperproliferative responses after bacterial infection (McConnell et al 2008) and KLF5 haploinsufficient (Klf5 C/K ) mice are protected from renal injury and inflammation induced by UUO (Fujiu et al 2011).…”

Section: Discussionmentioning

confidence: 69%

KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

Lappas¹

2015

Reproduction

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The transcription factor Kruppel-like factor 5 (KLF5) has been shown to associate with nuclear factor kappa B (NFkB) to regulate genes involved in inflammation. However, there are no studies on the expression and regulation of KLF5 in the processes of human labour and delivery. Thus, the aims of this study were to determine the effect of i) human labour on KLF5 expression in both foetal membranes and myometrium; ii) the pro-inflammatory cytokine interleukin 1 beta (IL1b), bacterial product flagellin and the viral dsRNA analogue poly(I:C) on KLF5 expression and iii) KLF5 knockdown by siRNA in human myometrial primary cells on pro-inflammatory and pro-labour mediators. In foetal membranes, there was no effect of term or preterm labour on KLF5 expression. In myometrium, the term labour was associated with an increase in nuclear KLF5 protein expression. Moreover, KLF5 expression was also increased in myometrial cells treated with IL1b, flagellin or poly(IC), likely factors contributing to preterm birth. KLF5 silencing in myometrial cells significantly decreased IL1b-induced cytokine expression (IL6 and IL8 mRNA expression and release), COX2 mRNA expression, and subsequent release of prostaglandins PGE 2 and PGF 2a . KLF5 silencing also significantly reduced flagellin-and poly(I:C)-induced IL6 and IL8 mRNA expression. Lastly, IL1b-, flagellin-and poly(I:C)-stimulated NFkB transcriptional activity was significantly suppressed in KLF5-knockout myometrial cells. In conclusion, this study describes novel data in which KLF5 is increased in labouring myometrium, and KLF5 silencing decreased inflammation-and infection-induced pro-labour mediators.

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Section: Discussionmentioning

confidence: 69%

KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

Lappas¹

2015

Reproduction

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“…17,18,29 Because the function of TNFAIP2 has never been studied in breast cancer, we first determined whether TNFAIP2 also promotes breast cancer cell proliferation. When TNFAIP2 was stably knocked down in HCC1937 cells using two different small hairpin RNA (shRNA) constructs (Figure 3a Figures S2C and D).…”

Section: Resultsmentioning

confidence: 99%

“…16 In breast cancer, KLF5 promotes cell proliferation and survival partially by upregulating the transcription of FGF-BP 17 and mPGES1. 18 In keratinocytes, KLF5 promotes cell migration by inducing transcription of integrin-linked kinase. 19 However, the function of KLF5 and the mechanism by which it exerts its effect have not been elucidated in the context of TNBC cell migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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“…In total, 80 samples (20 adjacent breast tissue samples and 60 invasive ductal breast carcinomas) were collected from the First Affiliated Hospital of the Kunming Medical University and stained. IHC was performed as previously described [19] with a standard diaminobenzidine (DAB) staining protocol. Briefly, antigens were first retrieved by boiling the slides in 0.1 M Tris-HCl ( pH 9.0) buffer for 5 min.…”

Section: Immunohistochemistry Stainingmentioning

confidence: 99%

Transforming growth factor-beta increases breast cancer stem cell population partially through upregulating PMEPA1 expression

Nie¹,

Wang²,

Zhou³

et al. 2016

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The prostate transmembrane protein, androgen-induced 1 (PMEPA1) has been previously shown to promote solid malignancies in a variety of cancers, but the role and mechanisms of PMEPA1 in breast cancer has not been fully addressed. Here, we found that PMEPA1 was upregulated in breast cancer cell lines as well as in a set of clinical invasive breast ductal carcinomas. Interestingly, depletion of PMEPA1 decreased breast cancer stem cell (CSC)-enriched populations, while ectopic overexpression of PMEPA1 increased breast CSC-enriched populations. Furthermore, transforming growth factor-β (TGF-β) treatment was also found to upregulate PMEPA1 expression and the CSCenriched populations in triple-negative breast cancer cell lines. TGF-β-induced PMEPA1 expression partially contributed to TGF-β-induced breast CSC maintenance. These findings suggest that TGF-β-PMEPA1 axis might provide new diagnosis and therapeutic targets for breast cancer treatment.

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Krüppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E2 Synthase 1 Gene Transcription in Breast Cancer

Cited by 43 publications

References 56 publications

KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

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

Transforming growth factor-beta increases breast cancer stem cell population partially through upregulating PMEPA1 expression

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