SwePub - sökning: WFRF:(van den Broek Maries)

Numrering	Referens	Omslagsbild	Hitta
1.	Zimmerli, Dario, et al. (författare) WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma 2018 Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 37:27, s. 3753-3762 Tidskriftsartikel (refereegranskat)abstract 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.

Zimmerli, Dario, et al. (författare)
WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma
2018
Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 37:27, s. 3753-3762
Tidskriftsartikel (refereegranskat)abstract
- 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.

Träfflista för sökning "WFRF:(van den Broek Maries) "