The High Mobility Group A1 (HMGA1) Chromatin Architectural Factor Modulates Nuclear Stiffness in Breast Cancer Cells
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Nano Innovation Laboratory, Elettra-Sincrotrone Trieste S.C.p.A., 34149 Trieste, Italy
Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Department of Infectious Diseases, Centre for Integrative Infectious Disease Research (CIID), Integrative Virology, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Present address: Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada.
Present address: Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Int. J. Mol. Sci. 2019, 20(11), 2733; https://doi.org/10.3390/ijms20112733
Received: 10 May 2019 / Revised: 28 May 2019 / Accepted: 30 May 2019 / Published: 4 June 2019
(This article belongs to the Special Issue HMG Proteins in Development and Disease)
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.