HER2 induces cell scattering and invasion through ∆Np63α and E-cadherin.

Abstract

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer constitutes approximately 30% of human breast cancers and is associated with poor outcomes. ∆Np63 is considered a metastasis inhibitor involved with cancer progression. This study aimed to clarify the roles and mechanisms of HER2 and ∆Np63 on scattering and invasion of MCF10A cells. Wild-type or mutant HER2 was cloned and transfected into MCF10A cells. Cell counting and transwell assays were applied to unveil the impact of HER2 upregulation and mutation on proliferation, cell scattering, and invasion. Western blotting and cell accounting were used to investigate the roles of ∆Np63 and p27. In vivo lung colonization assay was used to reveal the influences of HER2 and ∆Np63a on tumor metastasis. The results indicated HER2 remarkably enhanced cell proliferation, invasion, and scattering. Overexpression of either ΔNp63 or E-cadherin led to attenuated HER2-mediated regulation of cell migration, invasion, and scattering. Furthermore, we confirmed that HER2 enhanced cell proliferation but not migration through p27 and independent ∆Np63a. The results revealed that ∆Np63α contributed to the inhibition of HER2-induced metastasis. Collectively, our findings may further our understanding of the regulation of tumor progression and metastasis.