Consistently, many studies reported reduced expression of βCatenin and suppression of CSC proliferation in HNSCC upon treatment with inhibitors of the Wnt/βCatenin canonical pathway, including secreted FRP4 (frizzled-related protein), ATRA (all-trans-retionic acid) and honokiol, an active natural compound 51-53. This evidence concerns the gene SFRP4 and head and neck squamous cell carcinoma.