Oncogene, 2018-07, Vol.37 (27), p.3753-3762
2018
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- Autor(en) / Beteiligte
- Titel
- WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma
- Ist Teil von
- Oncogene, 2018-07, Vol.37 (27), p.3753-3762
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Human papillomavirus (HPV)-driven cutaneous squamous cell carcinoma (cSCC) is the most common cancer in immunosuppressed patients. Despite indications suggesting that HPV promotes genomic instability during cSCC development, the molecular pathways underpinning HPV-driven cSCC development remain unknown. We compared the transcriptome of HPV-driven mouse cSCC with normal skin and observed higher amounts of transcripts for Porcupine and WNT ligands in cSCC, suggesting a role for WNT signaling in cSCC progression. We confirmed increased Porcupine expression in human cSCC samples. Blocking the secretion of WNT ligands by the Porcupine inhibitor LGK974 significantly diminished initiation and progression of HPV-driven cSCC. Administration of LGK974 to mice with established cSCC resulted in differentiation of cancer cells and significant reduction of the cancer stem cell compartment. Thus, WNT/β-catenin signaling is essential for HPV-driven cSCC initiation and progression as well as for maintaining the cancer stem cell niche. Interference with WNT secretion may thus represent a promising approach for therapeutic intervention.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232, 1476-5594eISSN: 1476-5594DOI: 10.1038/s41388-018-0244-xTitel-ID: cdi_swepub_primary_oai_DiVA_org_liu_149856
- Format
- –
- Schlagworte
- 13/51, 38, 38/1, 38/39, 631/136/1425, 631/67/1813/1352, 64, 64/60, 96, 96/31, Acyltransferases - antagonists & inhibitors, Acyltransferases - metabolism, Animals, Apoptosis, Brief Communication, Cancer, Cancer cells, Carcinoma, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - pathology, Carcinoma, Squamous Cell - virology, Care and treatment, Cell Biology, Complications and side effects, Development and progression, Enzyme Inhibitors - pharmacology, Gene expression, Gene Expression Profiling, Genomic instability, Human Genetics, Human papillomavirus, Humans, Immunocompromised host, Internal Medicine, Ligands, Medicine, Medicine & Public Health, Membrane Proteins - antagonists & inhibitors, Membrane Proteins - metabolism, Mice, Neoplastic Stem Cells - pathology, Oncology, Papillomaviridae - genetics, Papillomaviridae - pathogenicity, Papillomavirus, Papillomavirus infections, Papillomavirus Infections - pathology, Physiological aspects, Pyrazines - pharmacology, Pyridines - pharmacology, Skin, Skin Neoplasms - genetics, Skin Neoplasms - pathology, Skin Neoplasms - virology, Skin tumors, Squamous cell carcinoma, Stem Cell Niche - physiology, Stem cells, Wnt protein, Wnt Proteins - metabolism, Wnt Signaling Pathway - genetics, β-Catenin