Dr Elena Rainero
Brief career history
Extracellular matrix internalisation in breast cancer
The extracellular matrix (ECM) is a complex network of secreted proteins which not only provides tissue support, but is also involved in the control of several cell functions, including migration and oncogenic transformation. The tumour microenvironment has a pivotal role in modulating cancer initiation, progression and metastasis, while cancer cells in turn modify the composition and properties of the ECM, demonstrating a bi-directional interaction between tumour and stroma. Our research addresses cell-ECM interaction from a novel and exciting angle, investigating how the internalisation of ECM components control breast cancer cell invasion.
Using a combination of different approaches, we aim at characterising the molecular mechanisms controlling ECM internalisation and how this process impinges on cancer cell growth and invasion.
The role of the extracellular matrix in supporting breast cancer cell metabolism
Altered cellular metabolism is one of the hallmarks of cancer. Due to tumour growth rate and limited blood supply, the tumour microenvironment is often hypoxic and deprived of nutrients (including glucose and amino acids). Cancer cells have been shown to use extracellular protein to support nutrient signalling and cell growth; however, the contribution of a complex 3D extracellular matrix (ECM) and its endocytosis to cancer cell growth and metabolism is very unclear.
Our lab is characterising the contribution of the extracellular matrix in fuelling breast cancer cell growth in 3D environments. Our preliminary data indicate that the presence of a collagen I, matrigel or laminin/entactin matrix is sufficient to rescue breast cancer cell growth in nutrient deprived conditions, in a way that requires ECM endocytosis. Interestingly, the ECM promotes cell growth/survival in the absence of amino acids or glucose, but not in serum, suggesting that the lack of specific nutrients can be compensated, at least in part, by the ECM. Furthermore, the ECM promotes cell proliferation under glutamine and amino acid starvation, but not serum or glucose. Taken together, these data suggest that the ECM can sustain cell growth/survival through different mechanisms depending on the specific starvation conditions.
We hypothesise that, under nutrient-deprived conditions, breast cancer cells use ECM internalisation and breakdown to support their proliferation/survival. To investigate this, we are assessing the contribution of complex 3D matrices and ECM receptors to cancer cell growth and elucidating whether ECM trafficking is driven by nutrient starvation. We will define how ECM internalisation impinges on cell metabolism and nutrient signalling and whether ECM-dependent
Undergraduate and postgraduate taught modules
Postgraduate studentship opportunities
We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com
For further information and details of other projects on offer, please see the department PhD Opportunities page:
- Rainero E (2018) Extracellular matrix internalization links nutrient signalling to invasive migration. International Journal of Experimental Pathology. View this article in WRRO
- Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C , Blyth K et al (2017) Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells. Nature Communications, 8. View this article in WRRO
- Rainero E (2016) Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer. Biochemical Society Transactions, 44(5), 1347-1354. View this article in WRRO
- Rainero E, Howe JD, Caswell PT, Jamieson NB, Anderson K, Critchley DR, Machesky L & Norman JC (2015) Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration. Cell Reports, 10(3), 398-413. View this article in WRRO
- Christoforides C, Rainero E, Brown KK, Norman JC & Toker A (2012) PKD Controls αvβ3 Integrin Recycling and Tumor Cell Invasive Migration through Its Substrate Rabaptin-5. Developmental Cell, 23(3), 560-572.
- Rainero E, Caswell PT, Muller PAJ, Grindlay J, McCaffrey MW, Zhang Q, Wakelam MJO, Vousden KH, Graziani A & Norman JC (2012) Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration. The Journal of Cell Biology, 196(2), 277-295. View this article in WRRO