Krüppel-like factors in cancer

Tétreault, Marie Pier; Yang, Yizeng; Katz, Jonathan P.

doi:10.1038/nrc3582

Cited by 336 publications

(348 citation statements)

References 200 publications

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“…Statistical analyses of the differentially expressed genes bound by KLF9 proximal to TSS showed that KLF9 functions primarily as a transcriptional repressor in the context of glioma neurospheres. This does not absolutely rule out the possibility that KLF9 has transactivating activity under defined biological contexts, particularly given the strong influence of biological context and genetic background on the gene regulatory activities, including those of KLF family members (24,55). A particularly relevant example is from Mitchell and DiMario (56), who found that KLF9 transactivated an FGFR1 promoterreporter construct in human myoblasts but repressed the same reporter in differentiated myotubes.…”

Section: Discussionmentioning

confidence: 99%

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

Ying

Tilghman

Wei

et al. 2014

Journal of Biological Chemistry

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Background: Cancer cell stemness determines tumor propagation and malignancy by poorly defined mechanisms. Results: The KLF9 transcription factor regulates cell fate and oncogenic pathways by repressing gene transcription in glioblastoma stem cells. Conclusion: KLF9 inhibits glioblastoma cell stemness and tumor growth by directly repressing genes, including ITGA6. Significance: KLF9 and its transcriptional network are potential targets for regulating cancer stem cells and glial malignancies.

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Section: Discussionmentioning

confidence: 99%

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

Ying

Tilghman

Wei

et al. 2014

Journal of Biological Chemistry

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“…29 To evaluate the correlation of other KLFs in TCGA lung adenocarcinoma, we analyzed mRNA expression level of KLF1-17 in adenocarcinoma patients and found that in addition to KLF4, KLF1, 2, 6, 8, 9, 10, 11, 12, 13, 14, 15 and 17 were also significantly lower in tumor compared with normal tissues (Supplementary Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to KLF4, other members of KLF family can be altered in lung cancers 29 ( Supplementary Figure 2). It is of great interest to further study the function of other KLF transcription factors in lung tumor initiation and progression.…”

mentioning

confidence: 99%

KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer

Chen

Zhang

et al. 2015

Cell Death Differ

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Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifeninduced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras LSL-G12D/+ ;Klf4 fl/fl mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

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“…In addition to the well-known functions of Klf4/5 in mammalian embryonic stem cells, other Klf proteins have been implicated in the regulation of cell proliferation, differentiation, and apoptosis and, hence, are essential for tissue and organ development. Aberrant expression of klf genes are linked to various diseases including cancers (Pearson et al, 2008;Cao et al, 2010;McConnell and Yang, 2010;Tetreault et al, 2013). A few studies so far have revealed that certain members in the Klf family are involved in early embryonic development through sea urchin to mouse (Howard et al, 2001;Gardiner et al, 2005;Yamazaki et al, 2008;Caiazzo et al, 2010;Lin et al, 2010;Kotkamp et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Kruppel‐like factor family genes are expressed during Xenopus embryogenesis and involved in germ layer formation and body axis patterning

Gao

Cao

Lü

et al. 2015

Developmental Dynamics

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Background: Kruppel-like factors (Klfs) are a family of transcription factors consisting of 17 members in mammals, Klf1-Klf17, which are involved in fundamental cellular physiological procedures, such as cell proliferation, differentiation, and apoptosis. However, their functions in embryonic development have been poorly understood. Our previous study has demonstrated that the pluripotency factor Klf4 participates in germ layer formation and axis patterning of Xenopus embryos by means of the regulation of key developmental signals. In the present study, we further investigated comprehensively the expression and functions of the klf family genes, klf2, klf5, klf6, klf7, klf8, klf11, klf15, and klf17, during the embryogenesis of Xenopus laevis. Results: Spatio-temporal expression analyses demonstrate that these genes are transcribed both maternally and zygotically in Xenopus embryos, and during organogenesis and tissue differentiation, they are localized to a variety of placodes and tissues. Gain and loss of function studies manifest that Klf factors play different roles in germ layer formation and body axis patterning. Moreover, each Klf factor exhibits distinct regulatory effects on the expression of genes that are essential for germ layer formation and body axis patterning. Conclusions: These results suggest that Klf factors are involved in the fine-tuning of these genes during early embryogenesis. Developmental Dynamics 244:1328-1346, 2015. V C 2015 Wiley Periodicals, Inc.

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Krüppel-like factors in cancer

Cited by 336 publications

References 200 publications

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

Kruppel-like Factor-9 (KLF9) Inhibits Glioblastoma Stemness through Global Transcription Repression and Integrin α6 Inhibition

KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer

Kruppel‐like factor family genes are expressed during Xenopus embryogenesis and involved in germ layer formation and body axis patterning

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