Screening and identification of small molecule inhibitors of ErbB2-induced invasion.

ABSTRACT: ERBB2 amplification and overexpression are strongly associated with invasive cancer with high recurrence and poor prognosis. Enhanced ErbB2 signaling induces cysteine cathepsin B and L expression leading to their higher proteolytic activity (zFRase activity), which is crucial for the invasion of ErbB2-positive breast cancer cells in vitro. Here we introduce a simple screening system based on zFRase activity as a primary readout and a following robust invasion assay and lysosomal distribution analysis for the identification of compounds that can inhibit ErbB2-induced invasion. With an unbiased kinase inhibitor screen, we identified Bohemine/Roscovitine, Gö6979 and JAK3 inhibitor VI as compounds that can efficiently decrease cysteine cathepsin activity. Using the well-established and clinica

SUBMITTER: Brix DM 

PROVIDER: S-EPMC5528609 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature