From Drosophila to Humans: MYC-Mediated Clone Competition as an Evolutionary Trait of Tumor Progression

Di Giacomo, Simone (2016) From Drosophila to Humans: MYC-Mediated Clone Competition as an Evolutionary Trait of Tumor Progression, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 28 Ciclo. DOI 10.6092/unibo/amsdottorato/7598.
Documenti full-text disponibili:
Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (11MB) | Anteprima


Cell competition describes the result of a mechanism of fitness comparison undertaken by cells inhabiting the same tissue, that leads to the elimination of the weakest cells and, in the physiology, to the formation of a homogeneous organ. Over the years, many molecules have been identified that are involved in cell competition and among them MYC oncoprotein: from Drosophila to mammals, cell populations characterised by higher expression of MYC induce apoptotic death of the neighbours, allowing the fittest to acquire an advantage in space occupancy. My work defined the presence of markers of MYC-mediated cell competition in primary and secondary human carcinomas and demonstrated through experiments in human cancer cell lines that MYC modulation is per se sufficient to induce competitive behaviours in both genetically distant and identical cells. Noteworthy, MYC under-regulation in the fittest cell line is sufficient to undermine its competitive status, suggesting a role for MYC-mediated cell competition in the selective growth of tumour clones and, as a consequence, in cancer evolution. In addition, I was able to demonstrate a functional cooperation between MYC and p53 in this phenomenon. The data obtained in the Drosophila model, where MYC over-expressing and MYC knock-down clones have been induced within a growing tumour, suggest that MYC-mediated cell competition is normally at work in these malignant cells, and it shapes cancer evolution through the elimination of the less fit cells (with lower levels of MYC) and the expansion of the most performant ones (with higher levels of MYC), demonstrating an evolutionary role played in defining the composition and the size of the final mass.

Tipologia del documento
Tesi di dottorato
Di Giacomo, Simone
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
MYC Cell-Competition Drosophila p53 Cancer Evolution
Data di discussione
22 Aprile 2016

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi