학술논문
ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression
Document Type
Article
Author
Rafn, Bo; Nielsen, Christian Friberg; Andersen, Sofie Hagel; Szyniarowski, Piotr; Corcelle-Termeau, Elisabeth; Valo, Erkka; Fehrenbacher, Nicole; Olsen, Charlotta Johanne; Daugaard, Mads; Egebjerg, Christina; Bøttzauw, Trine; Kohonen, Pekka; Nylandsted, Jesper; Hautaniemi, Sampsa; Moreira, José; Jäättelä, Marja; Kallunki, Tuula
Source
Subject
*PROTO-oncogenes
*CANCER cells
*CELLULAR signal transduction
*GENETICS of breast cancer
*ZINC-finger proteins
*CATHEPSIN B
*GENE expression
*PROTEIN-tyrosine kinases
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Language
ISSN
1097-2765
Abstract
Summary: Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified signaling network activates the transcription of cathepsin B gene (CTSB) via myeloid zinc finger-1 transcription factor that binds to an ErbB2-responsive enhancer element in the first intron of CTSB. This work provides a model system for ErbB2-induced breast cancer cell invasiveness, reveals a signaling network that is crucial for invasion in vitro, and defines a specific role and targets for the identified serine-threonine kinases. [Copyright &y& Elsevier]