Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer
- Madera, Santiago
- Izzo, Franco
- Chervo, María Florencia
- Dupont, Agustina
- Chiauzzi, Violeta Alicia
- Bruni, Sofia
- Petrillo, Ezequiel
- Merin, Sharon S.
- de Martino, Mara
- Montero, Diego
- Levit, Claudio
- Lebersztein, Gabriel
- Anfuso, Fabiana
- Roldán Deamicis, Agustina
- Mercogliano, María Florencia
- Proietti Anastasi, Cecilia Jazmín
- Schillaci, Roxana
- Elizalde, Patricia Virginia
- Cordo Russo, Rosalia Ines
DOIAbstract
Triple-negative breast cancer (TNBC) is clinically defined by the absence of estrogen and progesterone receptors and the lack of membrane overexpression or gene amplification of receptor tyrosine kinase ErbB-2/HER2. Due to TNBC heterogeneity, clinical biomarkers and targeted therapies for this disease remain elusive. We demonstrated that ErbB-2 is localized in the nucleus (NErbB-2) of TNBC cells and primary tumors, from where it drives growth. We also discovered that TNBC expresses both wild-type ErbB-2 (WTErbB-2) and alternative ErbB-2 isoform c (ErbB-2c). Here, we revealed that the inhibitors of the retrograde transport Retro-2 and its cyclic derivative Retro-2.1 evict both WTErbB-2 and ErbB-2c from the nucleus of BC cells and tumors. Usi...
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