The high mobility group A1 (HMGA1) chromatin architectural factor modulates nuclear stiffness in breast cancer cells

• Verfasst von: Senigagliesi, Beatrice [VerfasserIn]
• Verfasst von: Penzo, Carlotta [VerfasserIn]
• Titel: The high mobility group A1 (HMGA1) chromatin architectural factor modulates nuclear stiffness in breast cancer cells
• Verf.angabe: Beatrice Senigagliesi, Carlotta Penzo, Luisa Ulloa Severino, Riccardo Maraspini, Sara Petrosino, Hernan Morales-Navarrete, Enrico Pobega, Elena Ambrosetti, Pietro Parisse, Silvia Pegoraro, Guidalberto Manfioletti, Loredana Casalis and Riccardo Sgarra
• E-Jahr: 2019
• Jahr: 4 June 2019
• Umfang: 17 S.
• Fussnoten: Gesehen am 15.08.2019
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2019
• Band/Heft Quelle: 20(2019,11) Artikel-Nummer 2733, 17 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms20112733
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: atomic force microscopy (AFM)
• Sach-SW: cancer
• Sach-SW: chromatin
• Sach-SW: histone H1
• Sach-SW: HMGA1
• Sach-SW: mass spectrometry
• Sach-SW: nuclear stiffness
• Sach-SW: Stimulated emission depletion (STED) microscopy
• K10plus-PPN: 1671465202

Abstract

Plasticity is an essential condition for cancer cells to invade surrounding tissues. The nucleus is the most rigid cellular organelle and it undergoes substantial deformations to get through environmental constrictions. Nuclear stiffness mostly depends on the nuclear lamina and chromatin, which in turn might be affected by nuclear architectural proteins. Among these is the HMGA1 (High Mobility Group A1) protein, a factor that plays a causal role in neoplastic transformation and that is able to disentangle heterochromatic domains by H1 displacement. Here we made use of atomic force microscopy to analyze the stiffness of breast cancer cellular models in which we modulated HMGA1 expression to investigate its role in regulating nuclear plasticity. Since histone H1 is the main modulator of chromatin structure and HMGA1 is a well-established histone H1 competitor, we correlated HMGA1 expression and cellular stiffness with histone H1 expression level, post-translational modifications, and nuclear distribution. Our results showed that HMGA1 expression level correlates with nuclear stiffness, is associated to histone H1 phosphorylation status, and alters both histone H1 chromatin distribution and expression. These data suggest that HMGA1 might promote chromatin relaxation through a histone H1-mediated mechanism strongly impacting on the invasiveness of cancer cells.