Oncogenes, Transcription and Cancer
Bruno Amati
Group Leader
[email protected] | |
Location |
Building 13
Floor 1st Via Adamello 16, Milano |
The MYC proto-oncogene and its product, the MYC transcription factor, have a central role in cellular growth control and oncogenesis. In normal cells, MYC is induced by growth-promoting signals, and in turn regulates genes involved in key cellular responses (growth, proliferation, apoptosis, energy metabolism, biosynthetic pathways, etc…). During tumor development, a variety of oncogenic mutations (affecting either the MYC locus, or upstream signaling pathways) can elicit deregulated MYC expression and, as a consequence, the aberrant implementation of MYC-dependent gene expression programs. MYC-driven tumors show “oncogene addiction”, indicating that MYC itself – and presumably a subset of its target genes – are required for tumor maintenance.
Key questions in the field regard the mechanisms through which MYC regulates transcription, the identity of MYC-regulated genes, their function in growth control and tumorigenesis, as well as their potential as therapeutic targets.
Our research addresses these questions based on a combination of advanced biological models, high-throughput “omic” approaches and computational tools. In parallel with our basic research program, we pursue translational studies aimed at the development and pre-clinical validation of innovative therapeutic strategies.
Most Relevant Publications
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Donati G, Nicoli P, Verrecchia A, Vallelonga V, Croci O, Rodighiero S, Audano M, Cassina L, Ghsein A, Binelli G, Boletta A, Mitro N, Amati B
Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC-driven lymphoma.
EMBO Mol Med, 2023
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Donati G, Ravà M, Filipuzzi M, Nicoli P, Cassina L, Verrecchia A, Doni M, Rodighiero S, Parodi F, Boletta A, Vellano CP, Marszalek JR, Draetta GF, Amati B
Targeting mitochondrial respiration and the BCL2 family in high-grade MYC-associated B-cell lymphoma.
Mol Oncol, 2022
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Pellanda P, Dalsass M, Filipuzzi M, Loffreda A, Verrecchia A, Castillo Cano V, Thabussot H, Doni M, Morelli MJ, Soucek L, Kress T, Mazza D, Mapelli M, Beaulieu ME, Amati B, Sabò A
Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription.
EMBO J, 2021
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Rava' M, D'Andrea A, Nicoli P, Gritti I, Donati G, Doni M, Giorgio M, Olivero D, Amati B
Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma.
Sci Transl Med, 2018