Immunoprecipitation and subsequent immunoblotting also confirmed that the ubiquitination of HER3 decreased in both control and NOTCH1-knockdown SCCHN cells after treatment with wortmannin, which resulted in enhancement of USP8, and this suppression can be partially reversed by inhibition of USP8 through siRNA (Fig. 3E). Here, USP8 is linked to head and neck squamous cell carcinoma.