In vivo Wnt pathway inhibition of human squamous cell carcinoma growth and metastasis in the chick chorioallantoic model View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04-26

AUTHORS

Shannon F. Rudy, J. Chad Brenner, Jennifer L. Harris, Jun Liu, Jianwei Che, Megan V. Scott, John Henry Owen, Christine M. Komarck, Martin P. Graham, Emily L. Bellile, Carol R. Bradford, Mark EP Prince, Thomas E. Carey

ABSTRACT

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with poor overall survival. New therapeutic strategies that target specific molecular lesions driving advanced disease are needed. Herein we demonstrate the utility of the chicken chorioallantoic membrane (CAM) assay for in vivo human HNSCC tumor growth and metastasis and the tumor suppressive effects of a new chemotherapeutic agent. METHODS: We tested anti-metastatic effects of a WNT pathway inhibitor, WNT974 (also known as LGK974), which targets porcupine (PORCN) the palmityl-transferase that is essential for secretion of Wnt proteins. CAM assays were performed with 8 HNSCC cell lines: UM-SCC-1, UM-SCC-10A, UM-SCC-10B, UM-SCC-11A, UM-SCC-14A UM-SCC-17A, UM-SCC-17B, UM-SCC-25, and UM-SCC-34. RESULTS: UM-SCC-1 (University of Michigan Squamous Cell Carcinoma cell line) CAM xenografts contain CD44+ and ALDH+ cancer stem cell (CSC) proportions similar to UM-SCC-1 mouse xenografts supporting the applicability of the CAM assay for study of CSCs. Inhibition of WNT signaling by the PORCN inhibitor WNT974 reduced metastatic spread of UM-SCC cells, especially in UM-SCCs with Notch1 deficiency. CONCLUSIONS: Our data demonstrate decreased tumor growth and metastases in tumors from cell lines that showed in vitro responses to WNT974, providing evidence that this agent may have a role in future HNSCC therapy. More... »

PAGES

26

References to SciGraph publications

  • 2013-01-10. WNT branches out in NATURE REVIEWS CANCER
  • 2008-05. Wnt signalling and its impact on development and cancer in NATURE REVIEWS CANCER
  • 2003-02-18. Notch1 functions as a tumor suppressor in mouse skin in NATURE GENETICS
  • 2005-04. Wnt signalling in stem cells and cancer in NATURE
  • 2012-12-21. WNT signalling pathways as therapeutic targets in cancer in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40463-016-0140-8

    DOI

    http://dx.doi.org/10.1186/s40463-016-0140-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030094066

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27117272


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