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 Manuel Alfonso Moreira; Marja Jaattela; 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 Manuel Alfonso Moreira, Marja Jaattela, Tuula Kallunki

83 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
Journal	Molecular Cell
Volume	45
Issue number	6
Pages (from-to)	764-776
Number of pages	13
ISSN	1097-2765
DOIs	https://doi.org/10.1016/j.molcel.2012.01.029
Publication status	Published - 30 Mar 2012
Externally published	Yes

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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. M. A., Jaattela, 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

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, JMA, Jaattela, 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

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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 Moreira, {Jos{\'e} Manuel Alfonso} and Marja Jaattela and Tuula Kallunki",

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

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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

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 -

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

Abstract

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