Transcription factor–epigenetic crosstalk in cancer: integration of FOX networks and Hippo pathway dynamics

The field of cancer epigenetics examines how heritable changes in gene regulation - independent of DNA sequence - impact tumor biology. Recent advancements have highlighted the intricate interplay between transcription factor networks and epigenetic landscapes, particularly involving FOX family transcription factors and the Hippo pathway. These regulatory axes are essential for governing cell fate, proliferation, apoptosis, and metabolic adaptation in both solid and hematologic malignancies. However, they also underlie many aspects of cancer aggressiveness, such as metastasis, immune evasion, resistance to therapy, and disease recurrence. Ongoing research has begun to unravel how aberrant DNA methylation, dysregulated histone modifications, altered chromatin architecture, and changes in non-coding RNA expression converge on these networks, but the complexity and context-specific effects remain only partially understood.Significant studies have provided molecular insights into how FOX family members (for example, FOXO, FOXN, and FOXP) and Hippo pathway components (such as LATS2 and FAT4) control gene expression programs through interaction with epigenetic regulators and chromatin remodeling complexes. Current evidence suggests that these mechanisms integrate signals from changes in enhancer usage, chromatin accessibility, and non-coding RNA pathways to fine-tune cellular behavior. Novel high-throughput multi-omics technologies - including ATAC-seq, ChIP-seq, RNA-seq, and emerging single-cell and spatial methods - are clarifying the complexity of intratumoral heterogeneity and revealing potential regulatory vulnerabilities. Despite advances, gaps in the synthesis of these findings remain, particularly in linking specific epigenetic perturbations with actionable targets for intervention and in understanding the broader role of the tumor microenvironment on these networks.This Research Topic aims to advance our mechanistic and translational understanding of how epigenetic regulation coalesces with transcription factor networks - focusing on the FOX families and Hippo pathway - in dictating cancer cell phenotypes and responses to therapy. It seeks to stimulate the integration of cutting-edge multi-omics approaches and validation of pharmacologic or dietary modulators that can modify these axes. Additionally, the topic encourages exploration of novel biomarkers and translational strategies for personalized treatment and disease monitoring, as well as bridging tumor-intrinsic pathways with the broader microenvironmental and inflammatory cues that foster tumor evolution and resistance.This Research Topic covers the mechanistic, functional, and translational intersections between epigenetic regulation and FOX/Hippo signaling in cancer, with a focus on defining actionable nodes and biomarkers. Submissions that incorporate multi-omics and innovative experimental systems are particularly encouraged. To gather further insights in these areas, we welcome articles addressing, but not limited to, the following themes:Epigenetic modulation of FOX transcription factors and regulatory circuits in cancerHippo pathway–epigenome interactions shaping cancer chromatin landscapesNon-coding RNA and epi-transcriptomic networks controlling FOX/Hippo-driven cancer phenotypesMulti-omics, single-cell, and spatial mapping of intratumoral epigenetic heterogeneityEvaluation and validation of pharmacologic and phytochemical epigenetic modulators targeting FOX/Hippo axesDevelopment of biomarkers for prognosis, response prediction, or minimal residual disease tied to FOX/Hippo crosstalkIntegration of microenvironmental, inflammatory, and fibrosis-associated epigenetic signals with FOX/Hippo dynamicsSuitable article types include original research, brief reports, data reports, and reviews. Topic editors: Mohammad Aasif Khan, Kapil Dev, Sheersh Massey Source: https://www.frontiersin.org/research-topics/76819/transcription-factor-epigenetic-crosstalk-in-cancer-integration-of-fox-networks-and-hippo-pathway-dynamics