HMGA1 positively regulates the microtubule-destabilizing protein stathmin promoting motility in TNBC cells and decreasing tumour sensitivity to paclitaxel

• DOI: 10.1038/s41419-022-04843-4
• Publication Date: 2022-05-03T13:03:54Z
• Authors: Michela Sgubin; Silvia Pegoraro; Ilenia Pellarin; Gloria Ros; Riccardo Sgarra; Silvano Piazza; Gustavo Baldassarre; Barbara Belletti; Guidalberto Manfi...
• Keywords: Stathmin; Triple-negative breast cancer

Abstract High Mobility Group A1 (HMGA1) is an architectural chromatin factor involved in the regulation of gene expression and a master regulator Triple Negative Breast Cancer (TNBC). In TNBC, HMGA1 overexpressed coordinates network that controls cellular processes tumour development, progression, metastasis formation. Here, we find microtubule-destabilizing protein stathmin correlates breast cancer (BC) patients. We demonstrate depletion leads to downregulation activity on microtubules resulting decreased TNBC cell motility. show this pathway mediated by cyclin-dependent kinase inhibitor p27 kip1 (p27). Indeed, silencing cells results both increased stability p27-stathmin binding. When silenced, observe significant rescue These data, obtained models, were validated BC fact, patients with high levels low have statistically lower survival probability terms relapse-free (RFS) distant metastasis-free (DMFS) respect patient group HMGA1, stathmin, levels. Finally, vivo xenograft model chemo-sensitizes paclitaxel, drug commonly used treatments. This study unveils new interaction among p27, critical migration. Moreover, our data suggest taxol-based treatments may be more effective reducing burden when express HMGA1.