Journal Article

DKFZ-2026-02484

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png α7 integrin co-regulates chromatin accessibility and gene expression in HPV-negative head and neck cancer.

Borodins, O. ; Vehlow, A. ; Sameith, K. ; Dahl, A. ; Spangle, J. M. ; Aust, D. E. ; Brunner, C. ; Monni, O. ; Lange, I. ; Mircetic, J.DKFZ* ; Thomas, E. ; Cordes, N.DKFZ*

2026
Macmillan Publishers, part of Springer Nature London

Abstract: Epigenetic regulation and gene transcription are dynamically modulated by extracellular signals, including focal adhesions; however, the role of integrins in these processes remains poorly understood. In this study in HPV-negative head and neck squamous cell carcinoma, (HNSCC), we combined investigations in physiological three-dimensional, matrix-embedded cell models and patient-derived organoids 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 (ITGA7) emerged as the most potent modulator of histone post-translational modifications, associated with significant changes in gene transcription and chromatin accessibility. Depletion of ITGA7, achieved independently by CRISPR/Cas9 knockout and RNA interference, reduced chromatin accessibility at the AURKA locus and downregulated an AURKA-centered transcriptional program. 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. Across all analyses, machine-learning-based feature selection consistently nominated AURKA as the dominant downstream node, and tumor ITGA7 expression stratified patient overall survival in a non-linear manner. In summary, these findings establish α7 integrin as a key co-regulator of chromatin accessibility and gene transcription in HPV-negative HNSCC, acting through an AURKA-centered axis that couples adhesion signaling to cell cycle control and patient survival, and nominate AURKA, potentially targetable with clinical Aurora-A inhibitors such as alisertib, as an actionable therapeutic node downstream of the currently non-druggable ITGA7.

Keyword(s): Humans (MeSH) ; Integrin alpha Chains: genetics (MeSH) ; Integrin alpha Chains: metabolism (MeSH) ; Gene Expression Regulation, Neoplastic: genetics (MeSH) ; Chromatin: genetics (MeSH) ; Chromatin: metabolism (MeSH) ; Head and Neck Neoplasms: genetics (MeSH) ; Head and Neck Neoplasms: pathology (MeSH) ; Head and Neck Neoplasms: metabolism (MeSH) ; Human Papillomavirus Viruses: genetics (MeSH) ; Human Papillomavirus Viruses: pathogenicity (MeSH) ; Cell Line, Tumor (MeSH) ; Signal Transduction: genetics (MeSH) ; Squamous Cell Carcinoma of Head and Neck: genetics (MeSH) ; Squamous Cell Carcinoma of Head and Neck: pathology (MeSH) ; Squamous Cell Carcinoma of Head and Neck: metabolism (MeSH) ; Aurora Kinase A: genetics (MeSH) ; Antigens, CD (MeSH) ; Integrin alpha Chains ; Chromatin ; integrin alpha7 ; Aurora Kinase A ; Antigens, CD

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---