Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce miR-21 expression, PDCD4 downregulation and breast cancer metastasis
- Venturutti, Leandro
- Romero, Lucía Virginia
- Urtreger, Alejandro Jorge
- Chervo, María Florencia
- Cordo Russo, Rosalia Ines
- Mercogliano, María Florencia
- Inurrigarro, G.
- Pereyra, M. G.
- Proietti Anastasi, Cecilia Jazmín
- Izzo, Franco
- Díaz Flaqué, María Celeste
- Sundblad, Victoria
- Roa, J. C.
- Guzmán, P.
- Bal, Elisa Dora
- Charreau, Eduardo Hernan
- Schillaci, Roxana
- Elizalde, Patricia Virginia
DOIAbstract
Membrane overexpression of the receptor tyrosine kinase ErbB-2 (MErbB-2) accounts for a clinically aggressive breast cancer (BC) subtype (ErbB-2-positive) with increased incidence of metastases. We and others demonstrated that nuclear ErbB-2 (NErbB-2) also plays a key role in BC and is a poor prognostic factor in ErbB-2-positive tumors. The signal transducer and activator of transcription 3 (Stat3), another player in BC, has been recognized as a downstream mediator of MErbB-2 action in BC metastasis. Here, we revealed an unanticipated novel direction of the ErbB-2 and Stat3 interaction underlying BC metastasis. We found that Stat3 binds to its response elements (GAS) at the ErbB-2 promoter to upregulate ErbB-2 transcription in metastatic, E...
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