Krüppel-like factors in tumors: Key regulators and therapeutic avenues

Abstract

Krüppel-like factors (KLFs) are a group of DNA-binding transcriptional regulators with multiple essential functions in various cellular processes, including proliferation, migration, inflammation, and angiogenesis. The aberrant expression of KLFs is often found in tumor tissues and is essential for tumor development. At the molecular level, KLFs regulate multiple signaling pathways and mediate crosstalk among them. Some KLFs may also be molecular switches for specific biological signals, driving their transition from tumor suppressors to promoters. At the histological level, the abnormal expression of KLFs is closely associated with tumor cell stemness, proliferation, apoptosis, and alterations in the tumor microenvironment. Notably, the role of each KLF in tumors varies according to tumor type and different stages of tumor development rather than being invariant. In this review, we focus on the advances in the molecular biology of KLFs, particularly the regulations of several classical signaling pathways by these factors, and the critical role of KLFs in tumor development. We also highlight their strong potential as molecular targets in tumor therapy and suggest potential directions for clinical translational research.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

“…Adding to the epigenetic intricacy is the m6A RNA demethylase, FTO, which steers mRNA demethylation [ 32 ]. Such activity has been correlated with the destabilization of KLF3 mRNA, skewing cellular behavior towards osteosarcoma advancement and metastasis [ 33 ]. Recent studies suggest DNMT-1 inhibition can enhance the sensitivity of osteosarcoma cells to specific agents like cabozantinib.…”

Transgenerational Transmission of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Effects in Human Granulosa Cells: The Role of MicroRNAs

“…MiR-24-2-5p downregulation was significantly correlated with the upregulation of MYC that remained upregulated also on day 14 after chronic exposure. Krüppel-like factors (KLFs) are a group of DNA-binding transcriptional regulators with essential functions in various cellular processes, including proliferation, migration, inflammation, and angiogenesis [65]. KLF expression is often altered in tumors, and this is essential for tumor development.…”

“…KLF expression is often altered in tumors, and this is essential for tumor development. For instance, KLF8 is activated by transforming growth factor-β1 (TGF-β1) via SMAD2 and contributes to ovarian cancer progression [65,66]. Cherukunnath et al reported that the TGF-β1/SMAD2/KLF8 axis regulates epithelial-mesenchymal transition and contributes to ovarian cancer progression [66].…”

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