α7 integrin is a critical co-regulator of chromatin accessibility and gene expression in HPV-negative head and neck cancer

In this study in HPV-negative head and neck squamous cell carcinoma, we combined investigations in physiological 3-dimensional matrix cell models with multi-omics analyses, bioinformatics and artificial intelligence, to unmask the integrin effector signaling network that reshapes chromatin to drive cancer.

Among the 12 α/β1 integrin receptors, α7 integrin emerged as the most potent modulator of histone post-translational modifications, associated with significant changes in gene transcription and chromatin accessibility. Mechanistically, phosphoproteomics revealed significant inhibition of MAPK- and PI3K/AKT-dependent signaling with concomitant functional impairment of cell cycling and cell survival upon ITGA7 depletion.