Abstract

We have previously demonstrated that in Triple Negative Breast Cancer (TNBC), the most aggressive and with the worst prognosis among breast cancer subtypes, the architectural chromatin factor HMGA1 is overexpressed and coordinates a gene network that controls cellular processes involved in tumour development, progression, and metastasis formation. In this paper we found that the expression of HMGA1 and of the microtubule-destabilizing protein stathmin correlates in breast cancer (BC) patients. We demonstrate that HMGA1 depletion leads to a down-regulation of stathmin expression and activity on microtubules resulting in decreased TNBC cell motility. We show that this pathway is mediated by the cyclin-dependent kinase inhibitor p27^kip1 (p27). These data, obtained in cellular models, were validated in BC patients. Finally, we showed in an in vivo xenograft model that depletion of HMGA1 chemo-sensitizes tumour cells to paclitaxel, a drug that is commonly used in TNBC treatments. This study suggests that taxol-based treatments may be more effective in reducing the tumour burden when tumour cells express low levels of HMGA1.

The research involved the Chromatin and epigenetics in cancer of prof. Manfioletti in collaboration with that of dr. Belletti, Centro di Riferimento Oncologico (CRO), Aviano.