Medicine

A. Emre Sayan

PhD

Primary position:
Lecturer

Background

The University of Southampton

Dr Sayan holds a Molecular Biology and Genetics (MBG) degree from Bogazici University (Istanbul, 1995). Then he completed his MSc. (1997) and PhD. (2002) degrees in Bilkent University (Ankara). Between 2002 and 2010, he did 3 post-doctoral trainings in France (INSERM U370, Paris) and UK (MRC Toxicology Unit, Leicester and University of Leicester, CSMM dept). Dr Sayan was appointed as a lecturer in Cancer Sciences Division at University of Southampton in 2010.

His research (between 1997 and 2010) comprised the role of p53 family member proteins (p53, p63 and p73) during normal physiology and cancer development. Additionally he developed interest in Epithelial-Mesenchymal Transition (EMT), a process key to the spread of tumor cells, which is implicated in metastasis and chemo-resistance. As metastasis is the primary reason for cancer related death, identification and characterization of EMT pathways is critical for patient stratification and development of new therapies.

Dr. Sayan leads a group that investigates chemo-resistance and metastasis mechanisms in solid cancers. He has been specialized in hepatocellular carcinoma, bladder carcinoma, breast cancer and colorectal carcinoma. His research is based in Cancer Sciences Division, Southampton General Hospital and he has strong collaborations with clinical oncologists, consultants and surgeons. He has more than 25 peer-reviewed articles, most of which, in journals such as Oncogene, PNAS, Cell Death and Diff., JBC and JCB.

Qualifications

BSc, Bogazici University, Istanbul, Turkey (1995)
MSc, and PD. Bilkent University, Ankara, Turkey (1997 and 2002)

Dr A. Emre Sayan's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Moutasim, Karwan A., Mellows, Toby, Mellone, M., Lopez, Marie-Antoinette, Kiely, Phil, Sapienza, Karen, Greco, Azzura, Neill, Graham, Violette, Shelia, Weinreb, Paul, Marshall, John, Ottensmeier, Christian H., Sayan, A.E., Jenei, V. and Thomas, Gareth J. (2014) Suppression of hedgehog signalling promotes pro-tumourigenic integrin expression and function. The Journal of Pathology (doi:10.1002/path.4342). (PMID:24573955).
Bullock, M.D., Pickard, Karen M., Nielsen, B.S, Sayan, A.E., Jenei, Veronika, Mellone, Max, Mitter, R., Primrose, J.N., Thomas, Gareth J., Packham, Graham and Mirnezami, Alex H. (2013) Pleiotropic actions of mIR-21 highlight the critical role of deregulated stromal microRNA's during colorectal cancer progression. Cell Death and Disease, 4, e684. (doi:10.1038/cddis.2013.213). (PMID:23788041).
Bullock, M.D., Pickard, K.M., Nielsen, B.S., Sayan, A.E., Jenei, V., Mellone, M., Mitter, B., Primrose, J.N., Thomas, G.J., Packham, G.K. and Mirnezami, A.H. (2013) Pleiotropic actions of miR-21 highlight the critical role of deregulated stromal microRNAs during colorectal cancer progression. Cell Death and Disease, 4, e684. (doi:10.1038/cddis.2013.213). (PMID:23788041).
Sayan, A. Emre, Stanford, R., Vickery, R., Grigorenko, E., Diesch, J., Kulbichi, K., Mellon, J. K., Edwards, Richard, Pal, R., Greaves, P., Jariel-Encontre, I., Piechaczyk, M., Kriajevska, M. and Dhillon, A. S. (2012) Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL. Oncogene, 31, (12), 1493-1503. (doi:10.1038/onc.2011.336). (PMID:21822309).
Sayan, A. Emre, D'Angelo, Barbara, Sayan, Berna, Tucci, Paola, Cimini, AnnaMaria, Cerù, Maria Paola, Knight, Richard A. and Melino, Gerry (2010) p73 and p63 regulate the expression of fibroblast growth factor receptor 3. Biochemical and Biophysical Research Communications, 394, (3), 824-828. (doi:10.1016/j.bbrc.2010.03.084). (PMID:20298673).
Solyakov, L., Sayan, E., Riley, J., Pointon, A. and Tobin, A.B. (2009) Regulation of p53 expression, phosphorylation and subcellular localization by a G-protein-coupled receptor. Oncogene, 28, (41), 3619-3630. (doi:10.1038/onc.2009.225). (PMID:14601643).
Sayan, A Emre, Griffiths, Thomas R., Pal, Raj, Browne, Gareth J., Ruddick, Andrew, Yagci, Tamer, Edwards, Richard, Mayer, Nick J., Qazi, Hasan, Goyal, Sandeep, Fernandez, Serena, Straatman, Kees, Jones, George D.D., Bowman, Karen J., Colquhoun, Alexandra, Mellon, J Kilian, Kriajevska, Marina and Tulchinsky, Eugene (2009) SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America, 106, (35), 14884-14889. (doi:10.1073/pnas.0902042106). (PMID:18485877).
Sayan, A.E., Sayan, B.S., Gogvadze, V., Dinsdale, D., Nyman, U., Hansen, T.M., Zhivotovsky, B., Cohen, G.M., Knight, R.A. and Melino, G. (2008) P73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene, 27, (31), 4363-4372. (doi:10.1038/onc.2008.64). (PMID:18362891).
Hudson, C.D., Sayan, A.E., Melino, G., Knight, R.A., Latchman, D.S. and Budhram-Mahadeo, V. (2008) Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription. Cell Death and Differentiation, 15, (8), 1266-1278. (doi:10.1038/cdd.2008.45).
 

Research

Research Interests

Dr. Sayan’s research has a focus on general mechanisms of carcinoma development.

Mechanisms of Epithelial-Mesenchymal Transition and Cell Fate Control

EMT is a genetic trans-differentiation program when epithelial cells lose epithelial markers and become mesenchymal which results in enhanced cell motility and invasiveness. This developmentally important process is also implicated in wound healing, fibrosis and metastasis in adult life. More than 15 transcription factors functioning downstream of TGFb, Wnt and Notch signalling pathways have been identified to induce EMT. These transcription regulators belong to Zinc finger (SIP1, ZEB1, SNAIL, SLUG, SMUC, ATBF1, ZFH-5), basic Helix Loop Helix (TCF3, TCF4, Twist-1, Twist-2), Biocoid Subfamily (GSC1, GSC2) and DNA binding Forkhead Domain (FoxC1, FoxC2) family proteins (they will be referred as EMT-inducers from here on).

Recent data produced by us and others demonstrate a role for EMT inducers in pathways critical for cancer development. For example, SIP1 inhibits G1-S cell cycle progression through transcriptional repression of cyclin D1 and protects cancer cells from DNA damage-induced apoptosis. This effect on cell survival is associated with the reduced phosphorylation of ATM/ATR targets in response to DNA damage. SIP1 was also identified as one of the main transcriptional repressors of the catalytic subunit of telomerase (TERT). These results suggest that SIP1 up-regulation in cancer cells contributes to their survival and spread. However, in order to proliferate and evade senescence, cancer cells have to switch off SIP1 expression. Thus, a temporal control over SIP1 expression is essential for tumor progression.

These observations are in line with the functions of EMT inducers during development. EMT proceeds with decreased cell proliferation and resistance to apoptosis to make sure that the committed migrating cells will be quantitatively the same at destination. Migratory cells have a temporary cell cycle arrest because cell division and migration require different cyctoskeletal arrangements. On the other hand, developmental EMT induces resistance to apoptosis as migratory cells may have to go through potentially hostile environments before they settle down.

The aim of Sayan lab is to correlate the developmental functions of EMT inducers in cancer models and try to understand how cancer cells use EMT programs for their benefit.

Our key research questions are:

1- Do EMT programs regulate immune system to favour cancer growth?

2- Is there a cellular pathway that can be targeted to induce apoptosis only in mesenchymal but not in epithelial cells?

3- Which EMT inducers are specifically expressed in our carcinoma models and can they predict patient survival?

4- Do EMT programs regulate p53 family proteins to gain selective advantage?

For achieving our goals we are generating new reagents such as inducible cell lines, antibodies and shRNA constructs.

Academic unit:  Cancer Sciences Academic Unit

Affiliate academic units:  Human development and physiology Research group

Responsibilities


1- Postgraduate student supervision, Faculty of Medicine, University of Southampton

2- Reviewer for journals such as Oncogene, Cell Death and Diff, Cell Death and Dis, Nucleci Acid Research, etc.

Contact

Dr A. Emre Sayan
Phone: (023) 8120 5762
Fax: (023) 8120 5152
Email: a.e.sayan@soton.ac.uk