Higher expression of WNT5A protein in oral squamous cell carcinoma compared with dysplasia and oral mucosa with a normal appearance

WNT5A is a secreted signaling protein that promotes migration and invasion of oral squamous cell carcinoma (OSCC) cells through activation of non‐canonical WNT signaling. Here, we examined expression of WNT5A, β‐catenin, and E‐cadherin by immunohistochemistry in 21 human diagnostic incision biopsies that each had regions of oral mucosa with a normal appearance adjacent to the affected tissue, dysplasia, and OSCC. We also investigated the effect of recombinant WNT5A (rWNT5A) on expression of the cell‐adhesion proteins E‐cadherin and β‐catenin by western blot analysis. No expression of WNT5A protein was present in oral mucosa with a normal appearance or in mild grade dysplasia. However, expression of WNT5A increased along with increasing grade of dysplasia, and the highest expression was detected in OSCCs. Expression of membranous β‐catenin and of E‐cadherin was lower, whereas expression of cytoplasmic β‐catenin was higher, in OSCCs than in non‐cancerous regions. However, there was no correlation between expression of WNT5A and expression of either β‐catenin or E‐cadherin. Furthermore, treatment of OSCC cells with rWNT5A had no effect on the expression of β‐catenin or E‐cadherin. Taken together with previous results, we conclude that WNT5A influences the progression of OSCC without affecting the canonical WNT/β‐catenin pathway and without down‐regulating E‐cadherin. WNT5A may have potential as a biological marker for malignant transformation of dysplasia to OSCC.