The role of Krüppel-like factor 8 in cancer biology: Current research and its clinical relevance

Kumar, Sanjay; Behera, Abhijeet; Saha, Priyanka; Srivastava, Amit Kumar

doi:10.1016/j.bcp.2020.114351

Cited by 11 publications

(12 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our group found that previous nanotoxicological studies might ignore the importance of Kruppel‐like factors (KLFs). KLF family proteins are a set of C2H2 zinc finger TFs that can control many basic biological processes such as proliferation, differentiation, metabolism, and inflammation, and therefore, KLF proteins are widely involved in cancer biology, stem cell biology, and vascular biology (Gois Beghini et al, 2020; Kumar et al, 2021; C. Yang et al, 2021). The importance of KLFs can be revealed by the growth of publications in this field.…”

Section: Introductionmentioning

confidence: 99%

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Cao

2021

J of Applied Toxicology

View full text Add to dashboard Cite

The development of nanotechnology leads to the exposure of human beings to nanomaterials (NMs), and there is a health concern about the adverse vascular effects of NMs. Current data from epidemiology, controlled human exposure, and animal studies suggested that exposure to NMs could induce cardiopulmonary effects. In support of in vivo findings, in vitro studies showed that direct contact of vascular cells with NMs could induce endothelial cell (EC) activation and promote macrophage foam cell formation, although only limited studies showed that NMs could damage vascular smooth muscle cells and promote their phenotypic switch. It has been proposed that NMs induced adverse vascular effects via different mechanisms, but it is still necessary to understand the upstream events. Kruppel‐like factors (KLFs) are a set of C2H2 zinc finger transcription factors (TFs) that can regulate various aspects of vascular biology, but currently, the roles of KLF2 in mediating the adverse vascular effects of NMs have gained little attention by toxicologists. This review summarized current knowledge about the adverse vascular effects of NMs and proposed the potential roles of KLFs in mediating these effects based on available data from toxicological studies as well as the current understanding about KLFs in vascular biology. Finally, the challenges in investigating the role of KLFs in vascular toxicology were also summarized. Considering the important roles of KLFs in vascular biology, further studies are needed to understand the influence of NMs on KLFs and the downstream events.

show abstract

Section: Introductionmentioning

confidence: 99%

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Cao

2021

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…Among these TFs, LHX9 is an important steroidogenesis-related TF and indispensable for testis development ( Hu et al, 2018 ). KLF4 and KLF8 are Krüppel-like factors known to regulate several biological processes, such as cell proliferation, differentiation and metabolism ( Chu et al, 2016 ; Kult et al, 2021 ; Kumar et al, 2021 ). Similarly to KLF4, ARID5B also plays a pivotal role in adipogenesis and lipid metabolism, which might be closely related to cell differentiation and development ( Hata et al, 2013 ; Claussnitzer et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis

et al. 2022

View full text Add to dashboard Cite

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.

show abstract

“…3 KLF8 is a widely expressed transcription factor that belongs to the KLF family and regulates diverse cellular processes. 4,5 KLF8 consists of a highly conserved DNA-binding zinc finger domain that determines its functional specificity. KLF8 plays important transcriptional roles by binding to the target gene promoters through their DNA binding region.…”

Section: Introductionmentioning

confidence: 99%

“…KLF8 is a widely expressed transcription factor that belongs to the KLF family and regulates diverse cellular processes 4,5 . KLF8 consists of a highly conserved DNA‐binding zinc finger domain that determines its functional specificity.…”

Section: Introductionmentioning

confidence: 99%

KLF8 is activated by TGF‐β1 via Smad2 and contributes to ovarian cancer progression

Cherukunnath

Davargaon

Ashraf

et al. 2022

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Krüppel-like factor 8 (KLF8) is a transcription factor expressed abnormally in various cancer types and promotes oncogenic transformation. However, the role of KLF8 in ovarian cancer (OC) progression remains unclear. This study reports that transforming growth factor-β1 (TGF-β1)/Smad2/KLF8 axis regulates epithelial-mesenchymal transition (EMT) and contributes to OC progression. We analyzed the KLF8 expression in OC cells and tissues, wherein a significant overexpression of KLF8 was observed. Increased KLF8 expressions were correlated with higher cell proliferation, EMT, migration, and invasion and conferred poor clinical outcomes in OC patients. Overexpressed KLF8 increases F-actin polymerization and induces cytoskeleton remodeling of OC cells. Furthermore, a dissection of the molecular mechanism defined that TGF-β1 triggers KLF8 through the Smad2 pathway and regulates EMT. Pharmacological and genetic inhibition of Smad2 followed by TGF-β1 treatment failed to activate KLF8 expression and induction of EMT.Using promoter-luciferase reporter assays, we defined that upon TGF-β1 activation, phosphorylated Smad2 binds and promotes the KLF8 promoter activity, and knockdown of Smad2 inhibits KLF8 promoter activation. Together, these results demonstrate that TGF-β1 activates KLF8 expression by the Smad2 pathway, and KLF8 contributes to OC progression and may serve as a potential therapeutic strategy for treating OC patients.

show abstract

The role of Krüppel-like factor 8 in cancer biology: Current research and its clinical relevance

Cited by 11 publications

References 96 publications

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis

KLF8 is activated by TGF‐β1 via Smad2 and contributes to ovarian cancer progression

Contact Info

Product

Resources

About