ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression

Bo Rafn; Christian Friberg Nielsen; Sofie Hagel Andersen; Piotr Szyniarowski; Elisabeth Corcelle-Termeau; Erkka Valo; Nicole Fehrenbacher; Charlotta Johanne Olsen; Mads Daugaard; Christina Egebjerg; Trine Bøttzauw; Pekka Kohonen; Jesper Nylandsted; Sampsa Hautaniemi; José Moreira; Marja Jäättelä; Tuula Kallunki

doi:10.1016/j.molcel.2012.01.029

ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression

Bo Rafn
, Christian Friberg Nielsen
, Sofie Hagel Andersen
, Piotr Szyniarowski
, Elisabeth Corcelle-Termeau
, Erkka Valo
, Nicole Fehrenbacher
, Charlotta Johanne Olsen
, Mads Daugaard
, Christina Egebjerg
, Trine Bøttzauw
, Pekka Kohonen
, Jesper Nylandsted
, Sampsa Hautaniemi
, José Moreira
, Marja Jäättelä^*
, Tuula Kallunki^*

^*Corresponding author for this work

VTT Technical Research Centre of Finland

Danish Cancer Society
University of Helsinki
VTT (former employee or external)
University of Turku

Research output: Contribution to journal › Article › Scientific › peer-review

111 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	764-776
Journal	Molecular Cell
Volume	45
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2012.01.029
Publication status	Published - 2012
MoE publication type	A1 Journal article-refereed

Funding

This work was supported by the Danish Cancer Society, the Danish Medical Research Council, APO-SYS (EU Seventh Framework), the Danish National Research Foundation, Meyer Foundation, M.L. Jørgensen and Gunnar Hansens Foundation, Novo Nordisk Foundation, Danish Cancer Research Foundation, Alfred Benzon Foundation, Vilhelm Pedersen Foundation, and A Race Against Breast Cancer Foundation.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.molcel.2012.01.029

Cite this

Rafn, B., Nielsen, C. F., Andersen, S. H., Szyniarowski, P., Corcelle-Termeau, E., Valo, E., Fehrenbacher, N., Olsen, C. J., Daugaard, M., Egebjerg, C., Bøttzauw, T., Kohonen, P., Nylandsted, J., Hautaniemi, S., Moreira, J., Jäättelä, M., & Kallunki, T. (2012). ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Molecular Cell, 45(6), 764-776. https://doi.org/10.1016/j.molcel.2012.01.029

@article{05567b7be654437bb76dd656ac9526dc,

title = "ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression",

abstract = "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.",

author = "Bo Rafn and Nielsen, \{Christian Friberg\} and Andersen, \{Sofie Hagel\} and Piotr Szyniarowski and Elisabeth Corcelle-Termeau and Erkka Valo and Nicole Fehrenbacher and Olsen, \{Charlotta Johanne\} and Mads Daugaard and Christina Egebjerg and Trine B{\o}ttzauw and Pekka Kohonen and Jesper Nylandsted and Sampsa Hautaniemi and Jos{\'e} Moreira and Marja J{\"a}{\"a}ttel{\"a} and Tuula Kallunki",

year = "2012",

doi = "10.1016/j.molcel.2012.01.029",

language = "English",

volume = "45",

pages = "764--776",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "6",

}

Rafn, B, Nielsen, CF, Andersen, SH, Szyniarowski, P, Corcelle-Termeau, E, Valo, E, Fehrenbacher, N, Olsen, CJ, Daugaard, M, Egebjerg, C, Bøttzauw, T, Kohonen, P, Nylandsted, J, Hautaniemi, S, Moreira, J, Jäättelä, M & Kallunki, T 2012, 'ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression', Molecular Cell, vol. 45, no. 6, pp. 764-776. https://doi.org/10.1016/j.molcel.2012.01.029

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

AU - Jäättelä, Marja

AU - Kallunki, Tuula

PY - 2012

Y1 - 2012

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 - Article

SN - 1097-2765

VL - 45

SP - 764

EP - 776

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression

Abstract

Funding

UN SDGs

Access to Document

Fingerprint

Cite this