The Impact of MYC Modulation on Epithelial Cancer Evolution

Sollazzo, Manuela (2016) The Impact of MYC Modulation on Epithelial Cancer Evolution, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 30 Ciclo. DOI 10.6092/unibo/amsdottorato/8635.
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Despite MYC is one of the most referenced molecules in biology, new unanticipated roles are being found for this key protein, proving we are still far from understanding its full biological potential. During my PhD thesis, I investigated MYC function in a number of cancer traits using Drosophila larval organs as a model. Given that tumours develop in a complex landscape, where the entire cancer community continuously remodels local microenvironment, the conceptual scaffold of my work was built as to take into account both the cell-autonomous and non cell-autonomous MYC functions. The central findings of my study are: - Field cancerisation: I show that MYC, contrariwise to other growth-promoting molecules, is able to form a field where secondary mutations may originate multifocal cancers. This has great implication in human recurrent cancers. - Growth and migration/tracheogenesis: I show that MYC plays opposite but correlated roles in these two central cancer hallmarks: while it exerts a pro-growth effect following stabilisation by different upstream pathways, its presence inhibits cell migration by counteracting the JNK signalling. This has implication in cancer metastasis. - Cell competition/apoptosis: I show that apoptosis induced by MYC-mediated cell competition stimulates tumour growth; its inhibition indeed favours cancer collapse and prolongs animal life under heavy cancer burden. This has great implications in cancer treatment: while proapoptotic therapies may transiently reduce tumour mass, they may create a cytokine-rich environment which helps feed the tumour.

Tipologia del documento
Tesi di dottorato
Sollazzo, Manuela
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
MYC, Tracheogenesis, Cell competition, Drosophila, Field cancerisation, Apoptosis, Cancer
Data di discussione
18 Aprile 2016

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