Dr Ann Williams
Reader in Experimental Oncology
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12070 (internal 12070)
group: Cancer Research UK - Colorectal Tumour Biology group
Colorectal tumour cell survival mechanisms and chemoprevention
Despite epidemiological evidence to suggest that between 50-80% is preventable, colorectal cancer remains the second highest cause of cancer mortality in the UK. The central focus of my research group is to increase our understanding of key events in early colorectal carcinogenesis, including the importance of the tumour microenvironment for gene expression and function. The aim is to identify novel targets for chemoprevention which also have potential for adjuvant therapy.
Specific research interests:
- Dynamism in transcription factor function in response to microenvironmental stress provides new avenues for selective targeting of tumour cells and in this context, we have made the potentially exciting observation that BAG-1 (Bcl-2 associated athanogene) is a modulator of NF-κB signaling; this has implications for the regulation of a number of important pro-survival factors including the COX-2/prostaglandin, EGF and TGF-β pathways.
- We are particularly interested in the importance of the atypical p50 NF-κB homodimeric signalling pathway in colorectal carcinogenesis. We have shown that the Bcl-3/NF-κB homodimeric complex can promote tumour cell survival via an AKT dependent pathway. The focus is now on the importance of this complex in tumour stem cells.
- We are actively investigating the role of Bcl-3/NF-κB homodimeric complexes in colorectal cancer progression and the impact of Bcl-3 expression on patient prognosis.
- Our interest in NF-κB signaling has lead us to study the regulation of epithelial NF-κB signaling in inflammatory bowel disease. The aim is identify early markers of tumorigenic progression that could be used in the management of chronic bowel disease. In addition, in collaboration with David Morgan, we are investigating the role of epithelial NF-κB complexes in the innate tumour immune response.
- Petherick, K.J., Williams, A.C., Lane, J.D., Ordóñez-Morán, P., Huelsken, J., Smartt, H.J.M., Batson, J., Paraskeva, C. and Greenhough, A. (2013) A regulatory axis integrates Wnt/β-catenin-mediated suppression of autophagy and p62 expression with autophagic degradation of β-catenin. EMBO J. [Epub ahead of print]
- Al-Kharusi, M., Smartt, H.J.M., Greenhough, A., Collard, T.J., Emery, E., Williams, A.C. and Paraskeva, C. (2013) Lgr5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2: implications for targeting adenoma stem cells with NSAIDs. Carcinogenesis [Epub ahead of print]
- Skeen, V.R., Collard, T.J., Southern, S.L., Greenhough, A., Hague, A., Townsend, P.A., Paraskeva, C. and Williams, A.C. (2012) BAG-1 suppresses expression of the key regulatory cytokine transforming growth factor beta [TGF-β1] in colorectal tumour cells. Oncogene [Epub ahead of print].
- Skeen, V.R., Paterson, I., Paraskeva, C. and Williams, A.C. (2012) TGF-β1 Signalling, Connecting aberrant inflammation and colorectal tumorigenesis. Curr. Pharm. Des. 18(26): 3874-3888.
- Collard, T.J, Clemo, N.K., Urban, B., Hague, A., Townsend, P.A., Paraskeva, C. and Williams, A.C. (2012) The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the anti-apoptotic function of BAG-1 protein in colorectal tumour cells. Cell Death and Disease. 2012 [Epub ahead of print]
- Smartt, H.J., Greenhough, A., Ordóñez-Morán, P., Al-Kharusi, M., Collard, T.J., Mariadason, J.M., Huelsken, J., Williams, A.C. and Paraskeva, C.(2012) β-catenin negatively regulates expression of the prostaglandin transporter PGT in the normal intestinal epithelium and colorectal tumour cells: a role in the chemopreventive efficacy of aspirin? Br. J. Cancer 107(9), 1514-1517.
- Southern, S.L., Collard, T.J., Urban, B.C., Skeen, V.R., Smartt, H.J., Hague, A., Oakley, F., Townsend, P.A., Perkins, N.D., Paraskeva, C. and Williams, A.C. (2012) BAG-1 interacts with the p50-p50 homodimeric NF-κB complex: implications for colorectal carcinogenesis. Oncogene 31(22), 2761-2772.
- Smart, H.J., Greenhough, A., Ordóñez-Morán, P., Talero, E., Cherry, C.A., Wallam, C.A., Parry, L., Al Kharusi, M., Roberts, H.R., Mariadason, J.M., Clarke, A.R., Huelsken, J., Williams, A.C. and Paraskeva, C. (2011) β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells. Gut 61(9),1306-1314.
- Robinson, K.S., Clements, A., Williams, A.C., Berger, C.N. and Frankel, G. (2011) Bax Inhibitor 1 in apoptosis and disease. Oncogene 30(21), 2391-4000.
- Roberts, H.R., Smartt, H.J., Greenhough, A., Moore, A.E., Williams, A.C., Paraskeva, C. (2011) Colon tumour cells increase PGE(2) by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation. Carcinogenesis 32(11), 1741-1747.
- Greenhough, A., Wallam, C.A., Hicks, D.J., Moorghen, M., Williams, A.C. and Paraskeva, C. (2010) The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene. 29, 3398-410.
- Patsos, H.A., Greenhough, A., Hicks, D.J., Al Kharusi, M., Collard, T.J., Lane, J.D., Paraskeva, C. and Williams, A.C. (2010) The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells. Int. J. Oncol. 37, 187-93.
- Moore, A.E., Greenhough, A., Roberts, H.R., Hicks, D.J., Patsos, H.A., Williams, A.C. and Paraskeva, C. (2009) HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells. Carcinogenesis. 30,1796-1804.
- Greenhough, A., Smartt, H.J., Moore, A.E., Roberts, H.R., Williams, A.C., Paraskeva, C. and Kaidi, A. (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30(3), 377-86.
- Clemo, N.K., Collard, T.J., Southern, S., Edwards, K.D., Moorghen, M., Packham, G., Hague, A., Paraskeva, C. and Williams, A.C. (2008) BAG-1 is upregulated in colorectal tumour progression and promotes tumour cell survival through increased NF-kappaB activity. Carcinogenesis 29, 849-857.
View all publications held on the University of Bristol's IRIS database
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