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)
email: ann.c.williams@bristol.ac.uk
group: Cancer Research UK - Colorectal Tumour Biology group
Research interests
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 have previously identified BAG-1 as a pRb (tumour suppressor gene) binding protein. In collaboration with the Tissue engineering and stem cell therapies group, we are currently studying the role of this interaction in the determination of lineage commitment in stem cells.
- We have recently identified the mechanism by which BAG-1 can repress gene expression via the atypical p50 NF-κB homodimeric pathway. The focus is now on the importance of this interaction in tumour cell survival and tumour development. This has lead us to investigate the role of Bcl-3 in colorectal carcinogenesis and possible role in regulating the UPR under conditions relevant to the tumour microenvironment.
- 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 BAG-1 in the innate tumour immune response, investigating the potential for TGF-β1 mediated regulation of anti-tumour immunity.
Selected publications
- Robinson, K.S., Clements, A., Williams, A.C., Berger, C.N. and Frankel, G. (2011) Bax Inhibitor 1 in apoptosis and disease. Oncogene. Feb 7 [Epub ahead of print]
- 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.
- Hinitt, C.A., Wood, J., Lee, S.S., Williams, A.C., Howarth, J.L., Glover, C.P., Uney, J.B. and Hague, A. (2010) BAG-1 enhances cell-cell adhesion, reduces proliferation and induces chaperone-independent suppression of hepatocyte growth factor-induced epidermal keratinocyte migration. Exp. Cell. Res. 316, 2042-60.
- 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.
- Kaidi, A., Moorghen, M., Williams, A.C. and Paraskeva C. (2007) Is the downregulation of EphB2 receptor expression during colorectal tumorigenesis due to hypoxia? Gut 56, 1637-1638.
- Greenhough, A., Patsos, H.A., Williams, A.C. and Paraskeva C. (2007) The Cannabinoid Tetrahydrocannabinol, inhibits Ras-MAPK and PI3K- AKT survival signalling and induces BAD- mediated apoptosis in Colorectal Cancer Cells. Int. J. Cancer. 121, 2172-2180.
- Qualtrough, D., Kaidi, A., Chell, S., Jabbour, H.N., Williams, A.C. and Paraskeva, C. (2007) Prostaglandin F2 alpha stimulates motility and invasion in colorectal tumour cells. Int. J. Cancer. 121, 734-40.
- Kaidi, A., Williams, A.C., and Paraskeva, C. (2007) Interaction between β- catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat. Cell Biol. 9, 210-217.
- Lee, S.S., Crabb, S.J., Janghra, N., Carlberg, C., Williams, A.C., Cutress, R.I., Packham, G., Hague, A. (2007) Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: implications for oral carcinogenesis. Exp. Cell Res. 313(15), 3222-38.
- Williams, A.C., Smartt, H., H-Zadeh, A.M., Macfarlane, M., Paraskeva, C. and Collard, T.J. (2007). Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. Cell Death Differ., 14, 137-45.
View all publications held on the University of Bristol's IRIS database