Endocytic degradation of ErbB2 mediates the effectiveness of neratinib in the suppression of ErbB2-positive ovarian cancer.

Endocytic degradation of ErbB2 mediates the effectiveness of neratinib in the suppression of ErbB2-positive ovarian cancer. Int J Biochem Cell Biol. 2019 Nov 02;:105640 Authors: Wang S, Zhang J, Wang T, Feng R, Liu X, Lu Y, Xu L, Zhang Y, Wang D, Xu L, Wu Y, Liu F, Li Q, Zaky MY, Liu S, Dong W, Liu F, Zou K, Zhang Y Abstract The tyrosine kinase receptor ErbB2 is frequently found to be overexpressed in multiple cancer types. Targeted therapeutic approaches against ErbB2 have shown promising results and received FDA approvals in the treatment of breast cancer. However, this approach has not been granted in ovarian cancers till now. In order to assess the validity of ErbB2-targeted therapy in ovarian cancer, we investigated the effectiveness of two FDA-approved tyrosine kinase inhibitors of ErbB2, lapatinib and neratinib, on the growth of ovarian cancers. We observed that both lapatinib and neratinib displayed inhibitory effects towards the proliferation and migration of ErbB2-positive ovarian cancer cells in vitro, with neratinib showing stronger suppression in general. Neratinib treatment led to the reduction of ErbB2 protein levels, with concomitant attenuation of the phosphorylation of AKT, MEK, and ERK1/2. Immunofluorescence assays revealed that neratinib induced the internalization and lysosomal degradation of ErbB2, which was accompanied by its hyperubiquitylation. Lapatinib and neratinib also repressed the in vivo growth of SKOV...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research