KLF8 (Krüppel-like factor 8) is a transcription factor downstream of focal adhesion kinase (FAK) important in the regulation of the cell cycle and also plays a critical role in oncogenic transformation and epithelial to mesenchymal transition. Here we report the mechanisms by which FAK regulates KLF8 expression in human ovarian epithelial and cancer cells. We show that the overexpression of both KLF8 and FAK in the human ovarian cancer cells as compared with the normal human ovarian surface epithelial cells is critical for cell growth. Using promoter luciferase reporter assays, we demonstrate that exogenous FAK strongly promotes the activity of the KLF8 promoter, and knockdown of FAK inhibits it. KLF8 promoter activity and mRNA levels are induced by expression of constitutively active (CA) phosphatidylinositol 3-kinase (PI3K) or CA-Akt but are repressed by dominant negative Akt or the PI3K inhibitor LY294002. Disruption of an Sp1 binding site in the KLF8 promoter abolishes the FAK- or Sp1-mediated promoter activation. Sp1 knockdown prevents the KLF8 promoter from being activated by Sp1 or CA-Akt, and expression of CA-Akt enhances Sp1 expression in SKOV3ip1 cells. Chromatin immunoprecipitation and oligonucleotide precipitation results show that Sp1 binds to the KLF8 promoter. Taken together, our data suggest that FAK induces KLF8 expression in human ovarian cancer cells by activating the PI3K-Akt signaling pathway, leading to the activation of KLF8 promoter by Sp1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M709300200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Redefining prostate cancer risk stratification: a pioneering strategy to estimate outcome based on Ki67 immunoscoring.
Biomark Res
August 2024
Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/ CI-IPOP@ RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
Article Synopsis
- Accurate diagnosis and risk assessment for prostate cancer (PCa) patients is crucial for ensuring the best treatment outcomes, especially for those with low- and intermediate-risk disease who may opt for active surveillance (AS).
- A study developed risk calculators based on cancer biomarkers, such as Ki67 and KLF8 levels, to better distinguish which patients might benefit from more proactive interventions.
- The resulting prognostic model, known as ProstARK, showed promising accuracy in predicting biochemical recurrence-free survival, but further validation in larger studies is needed to confirm its effectiveness for patient selection in AS protocols.
KLF8 is activated by TGF-β1 via Smad2 and contributes to ovarian cancer progression.
J Cell Biochem
May 2022
Division of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, Andhra Pradesh, India.
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.
View Article and Find Full Text PDFOncogenic E3 ubiquitin ligase NEDD4 binds to KLF8 and regulates the microRNA-132/NRF2 axis in bladder cancer.
Exp Mol Med
January 2022
Department of General Surgery, the Fourth Affiliated Hospital of China Medical University, 110000, Shenyang, P.R. China.
The neuronally expressed developmentally downregulated 4 (NEDD4) gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation and has been implicated in tumor growth in various cancers. Hence, in this study, we intended to characterize the functional relevance of the NEDD4-mediated Kruppel-like factor 8/microRNA-132/nuclear factor E2-related factor 2 (KLF8/miR-132/NRF2) axis in the development of bladder cancer. NEDD4 and KLF8 were overexpressed in bladder cancer tissues and were associated with poorer patient survival rates.
View Article and Find Full Text PDFKnockdown of inhibits the differentiation of both intramuscular and subcutaneous preadipocytes in goat.
Anim Biotechnol
November 2023
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China.
elongs to the Krüppel-like factors (KLFs) family, which function as transcriptional regulators controlling a number of basic cellular processes, involving proliferation, differentiation, and migration. Here, we reveal insights into the differentiated expression of in different goat tissues and different stages of growth, and the inhibition role of knockdown to differentiation by using goat intramuscular and subcutaneous preadipocytes. We demonstrate that expression is obviously changed during the differentiation of preadipocytes into mature adipocytes.
View Article and Find Full Text PDFDiscovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer.
Cells
August 2020
Department of Urology, Medical University of Vienna, 1090 Vienna, Austria.
Background: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting.
Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!