ErbB-2 nuclear function in breast cancer growth, metastasis, and resistance to therapy
- P Elizalde, Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
- R Cordo Russo, Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
- M Chervo, Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
- R Schillaci, Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
- Correspondence: Patricia Elizalde, Email: pvelizalde{at}gmail.com
Abstract
Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ErbB-2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. Since a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular its role in growth, metastatic spreading, and response to currently available MErbB-2 positive BC therapies.
- Received 16 August 2016
- Revision received 3 October 2016
- Accepted 6 October 2016
- Accepted Preprint first posted online on 7 October 2016
