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 (Corresponding Author), Tuula Kallunki (Corresponding Author)

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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 languageEnglish
Pages (from-to)764-776
JournalMolecular Cell
Volume45
Issue number6
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Cathepsin B
Zinc Fingers
Breast Neoplasms
Protein Kinases
Cysteine
cdc42 GTP-Binding Protein
p21-Activated Kinases
Protein Kinase C-alpha
Cathepsin L
Cathepsins
Protein-Serine-Threonine Kinases
Receptor Protein-Tyrosine Kinases
Introns
Genes
Carrier Proteins
Transcription Factors
Phosphotransferases

Cite this

Rafn, B., Nielsen, C. F., Andersen, S. H., Szyniarowski, P., Corcelle-Termeau, E., Valo, E., ... 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
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. / ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. In: Molecular Cell. 2012 ; Vol. 45, No. 6. pp. 764-776.
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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",
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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

ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. / 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 (Corresponding Author); Kallunki, Tuula (Corresponding Author).

In: Molecular Cell, Vol. 45, No. 6, 2012, p. 764-776.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 45

SP - 764

EP - 776

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 6

ER -