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WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
Univ Zurich, Switzerland.
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2018 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 37, no 27, p. 3753-3762Article in journal (Refereed) Published
Abstract [en]

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/beta-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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 37, no 27, p. 3753-3762
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-149856DOI: 10.1038/s41388-018-0244-xISI: 000437975200011PubMedID: 29662191OAI: oai:DiVA.org:liu-149856DiVA, id: diva2:1236442
Note

Funding Agencies|Swiss National Science Foundation (SNF); Swiss Cancer League; Promedica Foundation Zurich; University of Zurich Research Priority Program "Translational Cancer Research"; Kanton of Zurich

Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-20

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Cantù, Claudio
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