Roles of Kr&amp;uuml;ppel-like factor 4 in normal homeostasis, cancer and stem cells

Evans, Paul M.; Liu, Chunming

doi:10.1111/j.1745-7270.2008.00439.x

Cited by 170 publications

(170 citation statements)

References 120 publications

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“…Kruppel-like factor 4 (Klf4) is a transcription factor expressed in a wide variety of tissues in humans and is important for many different physiological processes, including development, differentiation, and maintenance of normal tissue homeostasis [23]. Klf4 is a transcription factor that can either activate or repress transcription, depending on the target gene.…”

Section: Introductionmentioning

confidence: 99%

“…Klf4 is a transcription factor that can either activate or repress transcription, depending on the target gene. Klf4 can function as an oncogene or a tumor suppressor depending on the type of cancer involved [23]. Klf4 is an anti-proliferative factor in differentiated epithelia, and acts as a tumor suppressor in gastrointestinal cancers [24; 25].…”

Section: Introductionmentioning

confidence: 99%

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Embryonic stem cell markers expression in cancers

Schoenhals

Kassambara

Vos

et al. 2009

Biochemical and Biophysical Research Communications

221

202

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Abstract:The transcription factors Oct4 and Sox2 are highly expressed in embryonic stem (ES) cells. In conjunction with Klf4 and c-Myc, their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors are key regulators of the signaling network necessary for ES cell pluripotency. Self-renewal is a hallmark of stem cells and cancer and stemness program could play an important role in cancer.Therefore we compared the expression of Oct4, Sox2, Klf4 and c-Myc in 40 human tumor types to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.We found significant overexpression of at least 1/4 pluripotency factors Oct4, Sox2, Klf4 or c-Myc in 18 out of the 40 cancer types investigated. Furthermore, within a given tumor category these genes are associated with tumor progression or bad prognosis. A key goal in cancer research is to identify the mechanism by which cancer stem cells arise and self-renew. The overexpression of Oct3/4, Sox2, Klf4 and/or c-Myc could contribute to the pathologic self-renewal characteristics of cancer stem cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Embryonic stem cell markers expression in cancers

Schoenhals

Kassambara

Vos

et al. 2009

Biochemical and Biophysical Research Communications

221

202

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“…Kruppel-like factor 4 (KLF4/GKLF/EZF) encodes a transcription factor that is associated with both tumor suppression and oncogenesis (Evans and Liu 2008). Several lines of evidence indicate that KLF4 is an important regulator of cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα

et al. 2009

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Kruppel-like factor 4 (KLF4) is a transcription factor that participates in both tumor suppression and oncogenesis. To determine the association of KLF4 with tumorigenesis, we integrated data assembled in the Oncomine database and discovered a decrease in KLF4 gene transcripts in breast cancers. Further analysis of the database also showed a correlation between KLF4 expression and estrogen receptor-a (ERa) positivity. Knockdown of KLF4 in MCF-7 cells elevated the growth rate of these cells in the presence of estrogen. Therefore, we examined the interaction between KLF4 and ERa, and found that KLF4 bound to the DNA-binding region of ERa. KLF4 thus inhibits the binding of ERa to estrogen response elements in promoter regions, resulting in a reduction in ERa target gene transcription. Earlier studies have reported that KLF4 is transcriptionally activated by p53 following DNA damage. We also showed that activation of p53 decreased the transcriptional activity of ERa by elevating KLF4 expression. Our studies discovered a novel molecular network between p53, KLF4 and ERa. As both p53 and ERa are involved in cell growth and apoptosis, these results may explain why KLF4 possesses both tumor suppressive and oncogenic functions in breast cancers.

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“…activates and represses the transcription of different genes depending on the cellular context and thereby regulates numerous biological processes including proliferation, differentiation, development, inflammation, and apoptosis (1,2). In addition, KLF4 plays an important role in reprogramming differentiated somatic cells into induced pluripotent stem cells in both mouse and human (1).…”

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confidence: 99%