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.
