TY - JOUR
T1 - ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression
AU - Rafn, Bo
AU - Nielsen, Christian Friberg
AU - Andersen, Sofie Hagel
AU - Szyniarowski, Piotr
AU - Corcelle-Termeau, Elisabeth
AU - Valo, Erkka
AU - Fehrenbacher, Nicole
AU - Olsen, Charlotta Johanne
AU - Daugaard, Mads
AU - Egebjerg, Christina
AU - Bøttzauw, Trine
AU - Kohonen, Pekka
AU - Nylandsted, Jesper
AU - Hautaniemi, Sampsa
AU - Moreira, José Manuel Alfonso
AU - Jaattela, Marja
AU - Kallunki, Tuula
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/3/30
Y1 - 2012/3/30
N2 - 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.
AB - 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.
U2 - 10.1016/j.molcel.2012.01.029
DO - 10.1016/j.molcel.2012.01.029
M3 - Journal article
C2 - 22464443
SN - 1097-2765
VL - 45
SP - 764
EP - 776
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -
