Impact of autophagy on extracellular vesicle-mediated cell-to-cell communication in cancer

Anno
2020
Proponente Gian Maria Fimia - Professore Ordinario
Sottosettore ERC del proponente del progetto
LS3_7
Componenti gruppo di ricerca
Componente Categoria
Raffaele Strippoli Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Rossella Maione Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Francesca Ippolito Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Alessandra Marchetti Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Cecilia Battistelli Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Componente Qualifica Struttura Categoria
Claudia Montaldo Ricercatore sanitario Dipartimento di Epidemiologia, Ricerca Preclinica e Diagnostica avanzata, INMI Lazzaro Spallanzani IRCCS Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships
Fabiola Ciccosanti Ricercatore sanitario Dipartimento di Epidemiologia, Ricerca Preclinica e Diagnostica avanzata, INMI Lazzaro Spallanzani IRCCS Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships
Abstract

Tumour progression and metastasis formation relies on the ability of cancer cells to modify proximal and distal microenvironments in order to spread to other areas of the body. It is well established that extracellular vesicles (EVs) are pivotal in intercellular communication responsible for premetastatic niche formation. However, it is less characterized how tumour cells reprogram EV contents to favour their growth and dissemination.
This project takes the cue from recent evidence that autophagy, in addition to act as a survival process, is also involved in the regulation of EV loading and secretion.
This project aims to shed light on how autophagy impacts on the EV cargo sorting in tumour cells, and, in turn, on cell-to-cell communication in the context of cancer metastasis. In particular, we will focus our study on the role of autophagy in regulating the ability of EV released from colorectal cancer cells to promote the epithelial-to-mesenchymal transition (EMT) in hepatocytes.
The specific aims of this project will be:
1. To identify the molecular signatures underlying the autophagy-dependent compartmentalization of regulatory RNAs and RNA binding proteins in EVs produced by colorectal cancer cells.
2. To functionally characterize the role of autophagy-regulated EV RNAs released by colorectal cancer cells in promoting EMT of hepatocytes.
The characterization of the crosstalk between autophagy and EV sorting machinery here proposed will i) contribute to elucidate the molecular signalling responsible for premetastatic niche formation by tumour cells, and ii) disclose the therapeutic potential of inhibiting autophagy in tumour cells to interfere with cell-to-cell communication and prevent metastasis formation.

ERC
LS3_7, LS3_4, LS4_6
Keywords:
SEGNALAZIONE E INTERAZIONI CELLULARI, BASI BIOLOGICHE DEL CANCRO, BIOLOGIA CELLULARE

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