The high incidence of TMPRSS2:ERG fusion gene and ERG subsequent overexpression is still poorly characterized from a clinicopathologic point of view. This project aimed to investigate if ERG overexpression could be defined as a driver alteration that does the groundwork for tumour initiation, especially through a significant impact on tumour microenvironment. We aimed to identify differentially expressed and methylated genes that might be involved in tumour-tumour microenvironment crosstalk, ruling molecule trafficking and affecting stroma cells. Transcriptome analysis showed that ERG overexpression promoted IFN signalling activation, KRT deregulation and estrogenic response downregulation and highlighted the major role of STAT1 and its targets’ transcription. In addition, the DNA-seq analysis revealed that no significant DNA methylation occurred (at least in the selected cell model investigated), while a preliminary analysis on histone PTMs highlighted their pivotal role for ERG-dependent transcriptional programme, aimed to cell reprogramming. Notably, ERG-dependent transcriptional changes reflected on an altered secretome composition, influencing molecule secretion. In particular, the LC-MS analysis of conditioned media from cells overexpressing ERG stressed the significant enrichment of molecules involved in response to wounding, cell adhesion regulation, chemotaxis and extracellular matrix organization through complex secretory trafficking (both conventional and unconventional). Stroma cells exposed to ERG-induced CM showed an increased survival, suggesting that ERG overexpression played a role on molecule secretion in order to prompt tumour-tumour microenvironment crosstalk

L'overespressione di ERG promuove l'attivazione del signalling IFN, la deregolazione delle KRT e influenza la composizione del secretoma in un modello in vitro di tumore alla prostata / Maria Giovanna De Marino - : . , 2021. ((33. ciclo, Anno Accademico 2019/2020.

L'overespressione di ERG promuove l'attivazione del signalling IFN, la deregolazione delle KRT e influenza la composizione del secretoma in un modello in vitro di tumore alla prostata

DE MARINO MARIA GIOVANNA
2021

Abstract

The high incidence of TMPRSS2:ERG fusion gene and ERG subsequent overexpression is still poorly characterized from a clinicopathologic point of view. This project aimed to investigate if ERG overexpression could be defined as a driver alteration that does the groundwork for tumour initiation, especially through a significant impact on tumour microenvironment. We aimed to identify differentially expressed and methylated genes that might be involved in tumour-tumour microenvironment crosstalk, ruling molecule trafficking and affecting stroma cells. Transcriptome analysis showed that ERG overexpression promoted IFN signalling activation, KRT deregulation and estrogenic response downregulation and highlighted the major role of STAT1 and its targets’ transcription. In addition, the DNA-seq analysis revealed that no significant DNA methylation occurred (at least in the selected cell model investigated), while a preliminary analysis on histone PTMs highlighted their pivotal role for ERG-dependent transcriptional programme, aimed to cell reprogramming. Notably, ERG-dependent transcriptional changes reflected on an altered secretome composition, influencing molecule secretion. In particular, the LC-MS analysis of conditioned media from cells overexpressing ERG stressed the significant enrichment of molecules involved in response to wounding, cell adhesion regulation, chemotaxis and extracellular matrix organization through complex secretory trafficking (both conventional and unconventional). Stroma cells exposed to ERG-induced CM showed an increased survival, suggesting that ERG overexpression played a role on molecule secretion in order to prompt tumour-tumour microenvironment crosstalk
Prostate Cancer, ERG, IFN signalling, KRT
L'overespressione di ERG promuove l'attivazione del signalling IFN, la deregolazione delle KRT e influenza la composizione del secretoma in un modello in vitro di tumore alla prostata / Maria Giovanna De Marino - : . , 2021. ((33. ciclo, Anno Accademico 2019/2020.
File in questo prodotto:
File Dimensione Formato  
de Marino_PhD thesis_PDF_A.pdf

embargo fino al 09/03/2023

Tipologia: Tesi di dottorato
Licenza: Creative commons
Dimensione 29.26 MB
Formato Adobe PDF
29.26 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2115008
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact