The KLF4 Knockout 786-O Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the human KLF4 gene has been disrupted in the 786-O host cell background. This product provides a heterogeneous pool of edited cells, enabling loss-of-function studies of the zinc finger transcription factor KLF4 without the selection of a single clonal isolate. The polyclonal format captures a range of genetic modifications across the cell population, offering a robust model for investigating KLF4 function in a disease-relevant cellular context.
The 786-O cell line is a human renal cell adenocarcinoma line derived from a primary clear cell carcinoma. It harbors a frameshift mutation in the von Hippel-Lindau (VHL) tumor suppressor gene, leading to constitutive stabilization and activation of hypoxia-inducible factor 1-alpha (HIF-1??) and its downstream transcriptional program. Consequently, 786-O cells serve as a well-established model of VHL-deficient clear cell renal cell carcinoma (ccRCC), characterized by pseudohypoxic signaling, altered metabolism, and enhanced angiogenic factor expression.
KLF4 functions as a zinc finger transcription factor that plays critical roles in cell cycle regulation, differentiation, apoptosis, and maintenance of pluripotency. It is regulated by upstream factors including TGF-??1, p53, and microRNAs miR-143 and miR-145, and is influenced by hypoxia-mediated signaling. KLF4 transcriptionally activates downstream targets such as the cyclin-dependent kinase inhibitor p21 (CDKN1A) and the cell adhesion molecule E-cadherin (CDH1), while repressing genes that promote proliferation and mesenchymal phenotypes. Additionally, KLF4 interacts with key pluripotency factors SOX2, OCT4 (POU5F1), and c-MYC, and is modulated by co-regulators including p300/CBP, HDAC1, and SUZ12. Through these interactions, KLF4 integrates signals from pathways such as TGF-??/SMAD, Wnt/??-catenin, Notch, JAK/STAT, and p53, positioning it as a pivotal node in cellular homeostasis and tumor suppression.
In the VHL-deficient 786-O background, KLF4 is thought to function as a putative tumor suppressor, restraining oncogenic processes such as uncontrolled proliferation, epithelial-mesenchymal transition (EMT), and stemness. Its knockout removes transcriptional activation of p21 and E-cadherin, which may lead to enhanced cell cycle progression and loss of epithelial integrity. The loss of KLF4 is predicted to cooperate with constitutive HIF-1?? signaling to potentiate Wnt/??-catenin activity, potentially driving a more aggressive tumor phenotype. This model thus enables dissection of KLF4??s anti-tumor mechanisms and its crosstalk with hypoxic and growth factor pathways in ccRCC pathogenesis.
Researchers can employ this polyclonal knockout model for a wide range of experimental applications, including mechanistic studies of KLF4-dependent tumor suppression, EMT regulation, and stem cell-like properties in renal carcinoma. It is suitable for analyzing pathway modulation via Wnt/??-catenin, TGF-??/SMAD, and HIF-1??/VHL axes using techniques such as RNA sequencing, ChIP-qPCR for KLF4 target promoters, and co-immunoprecipitation with SOX2 or OCT4. Functional assays including MTT proliferation, apoptosis analysis, transwell migration and invasion, colony formation, and hypoxia response profiling can be performed to assess phenotypic outcomes. The model also supports drug response screening in VHL-mutant kidney cancer and comparative iPSC reprogramming studies. For further information regarding this product, please contact Ascent Research.
