Dr Elena Rainero

School of Biosciences

Lecturer

e.rainero@sheffield.ac.uk
+44 114 222 3696

B2-04, Florey Building, Firth Court

Full contact details

Dr Elena Rainero
School of Biosciences
B2-04, Florey Building
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

2016–present: Lecturer, The University of Sheffield (UK)
2015–2016: Research Fellow, The University of Sheffield (UK)
2009–2015: Post-doctoral researcher, the Beatson Institute for Cancer Research, Glasgow (UK)

Qualifications

2010: PhD in Human Biotechnology, University of Piemonte Orientale, Novara (Italy)
2006: Master Degree in Medical and Pharmaceutical Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)
2004: Bachelor Degree in Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)

Research interests

My group is interested in understanding the role of extracellular matrix internalisation in invasive cell migration and cell growth.

The extracellular matrix (ECM) is a complex network of secreted proteins that, beyond providing physical support to organs and tissues, regulates many cell functions, including proliferation, polarity, migration and oncogenic transformation.

Our aims are to understand the basic molecular events regulating ECM endocytosis, as well as how ECM uptake impinges on invasive cell migration and proliferation in complex 3D environments.

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
growth is promoted during carcinoma progression.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Nazemi M & Rainero E (2020) Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer. Frontiers in Oncology, 10. View this article in WRRO
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

All publications

Journal articles

Rainero E (2024) Macropinocytosis at the crossroad between nutrient scavenging and metabolism in cancer. Current Opinion in Cell Biology, 88, 102359-102359.
Yanes B & Rainero E (2022) The interplay between cell-extracellular matrix interaction and mitochondria dynamics in cancer. Cancers, 14(6).
Nazemi M & Rainero E (2020) Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer. Frontiers in Oncology, 10. View this article in WRRO
Llanses Martinez M & Rainero E (2019) Membrane dynamics in cell migration. Essays In Biochemistry. View this article in WRRO
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
Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell P, Campbel; A, Hogeweg A, Sansom O , Morton J et al (2017) Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. 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 & Norman JC (2015) Endosomal integrin signals for survival. Nature Cell Biology, 17(11), 1373-1375. 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
Macpherson IR, Rainero E, Mitchell LE, van den Berghe PVE, Speirs C, Dozynkiewicz MA, Chaudhary S, Kalna G, Edwards J, Timpson P & Norman JC (2014) CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer. Journal of Cell Science, 127(18), 3893-3901.
Rainero E & Norman JC (2013) Late endosomal and lysosomal trafficking during integrin-mediated cell migration and invasion. BioEssays, 35(6), 523-532.
Rizzolio S, Rabinowicz N, Rainero E, Lanzetti L, Serini G, Norman J, Neufeld G & Tamagnone L (2012) Neuropilin-1-Dependent Regulation of EGF-Receptor Signaling. Cancer Research, 72(22), 5801-5811.
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
Filigheddu N, Sampietro S, Chianale F, Porporato PE, Gaggianesi M, Gregnanin I, Rainero E, Ferrara M, Perego B, Riboni F , Baldanzi G et al (2011) Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30. Cellular Signalling, 23(12), 1988-1996.
Baldanzi G, Pighini A, Bettio V, Rainero E, Traini S, Chianale F, Porporato PE, Filigheddu N, Mesturini R, Song S , Schweighoffer T et al (2011) SAP-Mediated Inhibition of Diacylglycerol Kinase α Regulates TCR-Induced Diacylglycerol Signaling. The Journal of Immunology, 187(11), 5941-5951.
Rainero E & Norman JC (2011) New Roles for Lysosomal Trafficking in Morphogen Gradient Sensing. Science Signaling, 4(171), pe24-pe24.
Graziani A, Gaggianesi M, Porporato PE, Rainero E, Cianflone C, Ontano P, Pighini A, Chianale F, Chiorino G & Baldanzi G (2010) 754 DGKa, by regulating atypical PKC, is a key transducer of SDF1a-induced invasive behaviour in breast cancer cells. European Journal of Cancer Supplements, 8(5), 190-191.
Chianale F, Rainero E, Cianflone C, Bettio V, Pighini A, Porporato PE, Filigheddu N, Serini G, Sinigaglia F, Baldanzi G & Graziani A (2010) Diacylglycerol kinase mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI. Proceedings of the National Academy of Sciences, 107(9), 4182-4187.
Rainero E, Chianale F, Porporato PE, Cianflone C, Bettio V, Filigheddu N, Serini G & Graziani A (2009) HGF induces cell migration, ruffling and Rac activation through a novel signalling pathway coupling diacylglycerol kinase alpha to PKCz/i and RhoGDI. FEBS JOURNAL, 276, 250-250.
Baldanzi G, Cutrupi S, Chianale F, Gnocchi V, Rainero E, Porporato P, Filigheddu N, van Blitterswijk WJ, Parolini O, Bussolino F , Sinigaglia F et al (2008) Diacylglycerol kinase-α phosphorylation by Src on Y335 is required for activation, membrane recruitment and Hgf-induced cell motility. Oncogene, 27(7), 942-956.
Porporato PE, Rainero E, Chianale F, Ranaldo G, Arlandis GT, Locatelli I, Baldanzi G, Filigheddu N, Traini S, Gaggianesi M & Graziani A (2008) DIACYLGLYCEROL KINASE ALPHA IS REQUIRED FOR PROLIFERATION AND INVASION INDUCED BY GROWTH FACTORS AND CHEMOKINES. ANTICANCER RESEARCH, 28(5C), 3302-3303.
Chianale F, Cutrupi S, Rainero E, Baldanzi G, Porporato PE, Traini S, Filigheddu N, Gnocchi VF, Santoro MM, Parolini O , van Blitterswijk WJ et al (2007) Diacylglycerol Kinase-α Mediates Hepatocyte Growth Factor-induced Epithelial Cell Scatter by Regulating Rac Activation and Membrane Ruffling. Molecular Biology of the Cell, 18(12), 4859-4871.
Nazemi M, Yanes B, Martinez ML, Walker HJ, Pham K, Collins MO, Bard F & Rainero E () The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism. PLOS Biology, 22(1), e3002406-e3002406.
Rainero E, Cianflone C, Porporato PE, Chianale F, Malacarne V, Bettio V, Ruffo E, Ferrara M, Benecchia F, Capello D , Paster W et al () The Diacylglycerol Kinase α/Atypical PKC/β1 Integrin Pathway in SDF-1α Mammary Carcinoma Invasiveness. PLoS ONE, 9(6). View this article in WRRO
Nazemi M, Yanes B, Martinez ML, Walker H, Bard F & Rainero E () The extracellular matrix promotes breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism.

Chapters

Rainero E, van den Berghe PVE & Norman JC (2013) Internalisation, Endosomal Trafficking and Recycling of Integrins During Cell Migration and Cancer Invasion, Vesicle Trafficking in Cancer (pp. 327-359). Springer New York

Conference proceedings papers

Nan K & Rainero E (2020) Unravelling extracellular matrix endocytosis in breast cancer. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol. 101(3-4) (pp A4-A4)
Macpherson IR, Dornier E, Rabas N, Rainero E & Norman JC (2017) Abstract P6-01-06: Glutamine metabolism drives breast cancer invasion by providing a source of extracellular glutamate to activate the GRM3 metabotropic glutamate receptor. Cancer Research, Vol. 77(4 Supplement), 6 December 2016 - 10 December 2016. View this article in WRRO
Macpherson IR, Rainero E, van den Berghe PVE, Speirs C, Dozynkiewicz MA, Chaudhary S, Kalna G, Edwards J, Timpson P & Norman JC (2014) CLIC3 controls delivery of late endosomal MT1-MMP to the ventral plasma membrane and dictates invasion and metastasis in estrogen receptor-negative breast cancer. EUROPEAN JOURNAL OF CANCER, Vol. 50 (pp S112-S112)
Bettio V, Rainero E, Romano A, Bryant DM, Datta A, Mostov KE & Graziani A (2011) Diacilglycerol kinase alpha regulates central lumen formation through Annexin2 and Cdc42. FEBS JOURNAL, Vol. 278 (pp 141-141)
Cianflone C, Rainero E, Porporato PE, Chianale F, Gaggianesi M, Locatelli I, Ranaldo G, Baldanzi G & Graziani A (2010) Diacylglycerol kinase alpha regulates SDF1 alpha-induced cell invasion by regulating atypical PKC and matrix metallo proteinases 9. FEBS JOURNAL, Vol. 277 (pp 124-124)
Chianale F, Rainero E, Cianflone C, Bettio V, Pighini A, Porporato P, Filigheddu N, Serini G, Sinigaglia F, Baldanzi G & Graziani A (2010) Diacylglycerol Kinase alpha mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI. FEBS JOURNAL, Vol. 277 (pp 124-124)

Preprints

Llanses Martinez M, Nan K, Bao Z, Bacchetti R, Yuan S, Tyler J, Le Guezennec X, Bard FA & Rainero E (2024) Internalisation of integrin-bound extracellular matrix modulates invasive carcinoma cell migration, Cold Spring Harbor Laboratory.

Research group

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Teaching activities

Undergraduate:

BMS243 module co-ordinator
BMS243/247 Stem cells, aging and cancer
BMS379 Cancer Biology
Level 3 Practical and Dissertation Modules