Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy

Oppel F, Gendreizig S, Martinez-Ruiz L, Florido J, López-Rodríguez A, Pabla H, Loganathan L, Hose L, Kühnel P, Schmidt P, Schürmann M, et al. (2024)
Cell Death & Disease 15(10): 724.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Oppel, FelixUniBi; Gendreizig, SarahUniBi ; Martinez-Ruiz, Laura; Florido, Javier; López-Rodríguez, Alba; Pabla, Harkiren; Loganathan, Lakshna; Hose, LeonieUniBi ; Kühnel, PhilippUniBi ; Schmidt, PascalUniBi; Schürmann, MatthiasUniBi; Neumann, Judith MarthaUniBi
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Abstract / Bemerkung
Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have tumor-targeting potential. We modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by ATAC-seq and RNA-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. HNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound-healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue. Cornification was frequently found surrounding necrotic areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators activated the differentiation program in primary HNSCC cells. In HNSCC tissue, distinct cell differentiation states were found to create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon faithful HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection. © 2024. The Author(s).
Erscheinungsjahr
2024
Zeitschriftentitel
Cell Death & Disease
Band
15
Ausgabe
10
Art.-Nr.
724
eISSN
2041-4889
Page URI
https://pub.uni-bielefeld.de/record/2993270

Zitieren

Oppel F, Gendreizig S, Martinez-Ruiz L, et al. Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease. 2024;15(10): 724.
Oppel, F., Gendreizig, S., Martinez-Ruiz, L., Florido, J., López-Rodríguez, A., Pabla, H., Loganathan, L., et al. (2024). Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease, 15(10), 724. https://doi.org/10.1038/s41419-024-07065-y
Oppel, Felix, Gendreizig, Sarah, Martinez-Ruiz, Laura, Florido, Javier, López-Rodríguez, Alba, Pabla, Harkiren, Loganathan, Lakshna, et al. 2024. “Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy”. Cell Death & Disease 15 (10): 724.
Oppel, F., Gendreizig, S., Martinez-Ruiz, L., Florido, J., López-Rodríguez, A., Pabla, H., Loganathan, L., Hose, L., Kühnel, P., Schmidt, P., et al. (2024). Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease 15:724.
Oppel, F., et al., 2024. Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease, 15(10): 724.
F. Oppel, et al., “Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy”, Cell Death & Disease, vol. 15, 2024, : 724.
Oppel, F., Gendreizig, S., Martinez-Ruiz, L., Florido, J., López-Rodríguez, A., Pabla, H., Loganathan, L., Hose, L., Kühnel, P., Schmidt, P., Schürmann, M., Neumann, J.M., Ful, F.V., Scholtz, L.-U., Ligum, D., Brasch, F., Niehaus, K., Escames, G., Busche, T., Kalinowski, J., Goon, P., Sudhoff, H.: Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease. 15, : 724 (2024).
Oppel, Felix, Gendreizig, Sarah, Martinez-Ruiz, Laura, Florido, Javier, López-Rodríguez, Alba, Pabla, Harkiren, Loganathan, Lakshna, Hose, Leonie, Kühnel, Philipp, Schmidt, Pascal, Schürmann, Matthias, Neumann, Judith Martha, Ful, Flavian Viyof, Scholtz, Lars-Uwe, Ligum, Dina, Brasch, Frank, Niehaus, Karsten, Escames, Germaine, Busche, Tobias, Kalinowski, Jörn, Goon, Peter, and Sudhoff, Holger. “Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy”. Cell Death & Disease 15.10 (2024): 724.

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