Krüppel-like Factor 4 Inhibits Tumorigenic Progression and Metastasis in a Mouse Model of Breast Cancer

Yori, Jennifer L.; Seachrist, Darcie D.; Johnson, Emhonta; Lozada, Kristen L.; Abdul‐Karim, Fadi W.; Chodosh, Lewis A.; Schiemann, William P.; Keri, Ruth A.

doi:10.1593/neo.11260

Cited by 109 publications

(99 citation statements)

References 46 publications

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“…Thus, in invasive ductal breast carcinoma increased KLF4 nuclear staining is associated with poor prognosis [14]. However, KLF4 was recently shown to inhibit tumor progression in a xenograft animal model [15] and EMT in vitro [11]. KLF4 accordingly up-regulates E-cadherin expression.…”

Section: Introductionmentioning

confidence: 99%

Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression

Koopmansch

Berx

Foidart

et al. 2013

Biochemical and Biophysical Research Communications

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a b s t r a c t E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. We have here explored a potential competition between ZEB2 and KLF4 for the binding to the E-cadherin promoter. We show an inverse correlation between ZEB2 expression levels and KLF4 recruitment on the E-cadherin promoter in three breast cancer cell lines and in A431/HA.ZEB2 cells in which ZEB2 expression is induced by doxycycline (DOX). We identified a region of the E-cadherin promoter bound by KLF4 which is necessary for the activation of the E-cadherin promoter activity after KLF4 overexpression. This region is localized between positions À28 and À10 and thus overlaps with one of the ZEB2 binding sites. Deleting the bipartite ZEB2 binding site results in increased KLF4 induced E-cadherin promoter activity. Taken together, our results suggest that E-cadherin expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels.

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Section: Introductionmentioning

confidence: 99%

Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression

Koopmansch

Berx

Foidart

et al. 2013

Biochemical and Biophysical Research Communications

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“…Similarly to the inhibitory effects of the KLF4 gene on breast cancer progression, Yori et al (15) revealed that KLF4 overexpression in human breast cancer MDA-MB-231 cells upregulated the protein and mRNA levels of E-cadherin, which were decreased by interfering with its expression. Yori et al (25) also reported that KLF4 inhibited the invasion and distal metastasis of breast cancer by suppressing epithelial-mesenchymal transition.…”

Section: Discussionmentioning

confidence: 96%

Expression of Krüppel-like factor 4 in breast cancer tissues and its effects on the proliferation of breast cancer MDA-MB-231 cells

Song

Xing

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to detect the expression of Krüppel-like factor 4 (KLF4) in breast cancer tissues and to evaluate the effect on the proliferation of breast cancer MDA-MB-231 cells. The expression of KLF4 protein in 239 breast cancer tissues and 40 paracancerous tissues were detected by an immunohistochemical assay, and its correlation with clinical pathological parameters was analyzed. A eukaryotic expression vector, pcDNA3.1-KLF4, was constructed by transient transfection of breast cancer MDA-MB-231 cells with liposomes (experimental group). The untransfected cells and those transfected with empty plasmid pcDNA3.1 were used as the blank and negative control groups, respectively. The expression of the KLF4 gene and protein in the three groups were detected by reverse transcription polymerase chain reaction and western blotting, respectively. Furthermore, the cell proliferative capacity was detected by an MTT assay. The positive expression rate of KLF4 protein in breast cancer tissues (39.0%, 93/239) was significantly lower than that of paracancerous tissues (77.5%, 31/40) (P<0.05). In addition, KLF4 protein expression in breast cancer tissues was correlated with pathological type, histological grade and lymphatic metastasis (P<0.05). KLF4 mRNA and protein were both expressed by the experimental group, but not by the two control groups. Meanwhile, the proliferative capacity of the experimental group was also significantly decreased. A significant decrease in the positive expression rate of KLF4 protein in breast cancer tissues was correlated with several clinical pathological parameters. In addition, transfection of the KLF4 gene inhibited the proliferation of breast cancer cells, suggesting that this gene is important in the onset and progression of this type of cancer.

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“…Downregulation of KLF4 decreases tumor formation in vivo, while overexpression of KLF4 increases CSC population (Yu et al, 2011). Therefore, it seems that KLF4 can suppress the EMT process and inhibit metastasis in breast cancer cells (Yori et al, 2010(Yori et al, , 2011, however, it can also induce CSC-like properties to promote metastasis and invasion. In lung cancer cell lines, inhibition of KLF4 by Numb-like protein (NUMBL) maintains progenitor-like cells (Vaira et al, 2013).…”

Section: Role Of Klf4 In Cscsmentioning

confidence: 99%

Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

Ding¹,

Liu²,

Li³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of KLF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

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Krüppel-like Factor 4 Inhibits Tumorigenic Progression and Metastasis in a Mouse Model of Breast Cancer

Cited by 109 publications

References 46 publications

Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression

Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression

Expression of Krüppel-like factor 4 in breast cancer tissues and its effects on the proliferation of breast cancer MDA-MB-231 cells

Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

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