HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
1
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
2
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
*
Authors to whom correspondence should be addressed.
†
Present addresses: Department of Infectious Diseases, Centre for Integrative Infectious Disease Research (CIID), Integrative Virology, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
‡
United World College of the Adriatic, Duino Aurisina (TS), Trieste, 34011, Italy.
Cancers 2019, 11(8), 1105; https://doi.org/10.3390/cancers11081105
Received: 21 May 2019 / Revised: 19 July 2019 / Accepted: 29 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Epigenetic Dysregulation in Cancer: From Mechanism to Therapy)
Abstract
Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers. View Full-TextKeywords:
High Mobility Group A; breast cancer; TNBC; epigenetic; RSK2; CBP; histone H3; histone H2B
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Penzo, C.; Arnoldo, L.; Pegoraro, S.; Petrosino, S.; Ros, G.; Zanin, R.; Wiśniewski, J.R.; Manfioletti, G.; Sgarra, R. HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells. Cancers 2019, 11, 1105.
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