The extracellular matrix (ECM) is one of the major structural components of the tumour microenvironment, and it is mainly composed of collagen molecules. During tumorigenesis the ECM undergoes a profound remodelling to sustain cancer cell aggressiveness. Nevertheless, the molecular mechanisms that orchestrate the ECM remodelling are largely unclear. Recent evidence suggests the existence of a link between the ECM composition and the metabolic state of cancer cells. Cancer cells rewire glutamine (Gln) metabolism to promote tumour progression and, Gln is a precursor of Proline, one of the most abundant amino acids found in collagens. My laboratory has previously shown that the mitochondrial chaperone TRAP1 is a master regulator of metabolic circuits in cancer cells, and cells lacking TRAP1 show lower collagen VI (col VI) levels. In the framework of my thesis, I investigated whether changes in amino acid metabolism sustain cancer cell tumorigenicity by tuning the ECM composition, and the role played by TRAP1 in this process. To this aim, I perfomed several in vitro tumorigenic assays in cancer cells from an aggressive tumour of the peripheral nerve sheath (MPNST). I found that: i) Gln availability influences MPNST proliferation; ii) both TRAP1 and Col VI affect MPNST cell migration and invasion.
The extracellular matrix (ECM) is one of the major structural components of the tumour microenvironment, and it is mainly composed of collagen molecules. During tumorigenesis the ECM undergoes a profound remodelling to sustain cancer cell aggressiveness. Nevertheless, the molecular mechanisms that orchestrate the ECM remodelling are largely unclear. Recent evidence suggests the existence of a link between the ECM composition and the metabolic state of cancer cells. Cancer cells rewire glutamine (Gln) metabolism to promote tumour progression and, Gln is a precursor of Proline, one of the most abundant amino acids found in collagens. My laboratory has previously shown that the mitochondrial chaperone TRAP1 is a master regulator of metabolic circuits in cancer cells, and cells lacking TRAP1 show lower collagen VI (col VI) levels. In the framework of my thesis, I investigated whether changes in amino acid metabolism sustain cancer cell tumorigenicity by tuning the ECM composition, and the role played by TRAP1 in this process. To this aim, I perfomed several in vitro tumorigenic assays in cancer cells from an aggressive tumour of the peripheral nerve sheath (MPNST). I found that: i) Gln availability influences MPNST proliferation; ii) both TRAP1 and Col VI affect MPNST cell migration and invasion.
Investigating the interplay between extracellular matrix and metabolic rewiring in sarcoma aggressiveness
SBUELZ, FRANCESCA
2023/2024
Abstract
The extracellular matrix (ECM) is one of the major structural components of the tumour microenvironment, and it is mainly composed of collagen molecules. During tumorigenesis the ECM undergoes a profound remodelling to sustain cancer cell aggressiveness. Nevertheless, the molecular mechanisms that orchestrate the ECM remodelling are largely unclear. Recent evidence suggests the existence of a link between the ECM composition and the metabolic state of cancer cells. Cancer cells rewire glutamine (Gln) metabolism to promote tumour progression and, Gln is a precursor of Proline, one of the most abundant amino acids found in collagens. My laboratory has previously shown that the mitochondrial chaperone TRAP1 is a master regulator of metabolic circuits in cancer cells, and cells lacking TRAP1 show lower collagen VI (col VI) levels. In the framework of my thesis, I investigated whether changes in amino acid metabolism sustain cancer cell tumorigenicity by tuning the ECM composition, and the role played by TRAP1 in this process. To this aim, I perfomed several in vitro tumorigenic assays in cancer cells from an aggressive tumour of the peripheral nerve sheath (MPNST). I found that: i) Gln availability influences MPNST proliferation; ii) both TRAP1 and Col VI affect MPNST cell migration and invasion.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/79740