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Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: Implications for targeting cancer stem cells (2015)
Journal Article
Williams, A. C., Paraskeva, C., Greenhough, A., Lane, J. D., Collard, T. J., Jones, R. F., …Williams, A. C. (2015). Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: Implications for targeting cancer stem cells. British Journal of Cancer, 112(4), 714-719. https://doi.org/10.1038/bjc.2015.4

© 2015 Cancer Research UK. Background:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenv... Read More about Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: Implications for targeting cancer stem cells.

Circulating prostaglandins as biomarkers for colorectal cancer? (2015)
Journal Article
Williams, A. C., Greenhough, A., Paraskeva, C., & Williams, A. C. (2015). Circulating prostaglandins as biomarkers for colorectal cancer?. EBioMedicine, 2(2), 105-106. https://doi.org/10.1016/j.ebiom.2015.01.016

Despite increases in our understanding of intestinal tumour biology, colorectal cancer remains a leading cause of cancer-related death worldwide. Most colorectal cancers develop from benign adenomas, presenting an opportunity for early detection and... Read More about Circulating prostaglandins as biomarkers for colorectal cancer?.

Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells (2014)
Journal Article
Malik, K., Deery, M. J., Brown, K. W., Heesom, K. J., Melegh, Z., Vieira, G. C., …Malik, K. T. (2015). Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells. Molecular Oncology, 9(3), 617-627. https://doi.org/10.1016/j.molonc.2014.10.015

© 2014 The Authors. Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and MYCN over-expression. Here we present data showing that short-interfering RNA mediated depletion of the prote... Read More about Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk (2013)
Journal Article
Collard, T. J., Lane, J. D., Williams, A. C., Petherick, K. J., Petherick, K. J., Williams, A. C., …Greenhough, A. (2013). Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk. EMBO Journal, 32(13), 1903-1916. https://doi.org/10.1038/emboj.2013.123

The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both basal and stress-induc... Read More about Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk.

LGR5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2: Implications for targeting adenoma stem cells with nsaids (2013)
Journal Article
Williams, A. C., Emery, E. D., Collard, T. J., Smartt, H. J., Al-Kharusi, M. R., Al-Kharusi, M. H., …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, 34(5), 1150-1157. https://doi.org/10.1093/carcin/bgt020

Cyclooxygenase-2 is overexpressed in the majority of colorectal tumours leading to elevated levels of prostaglandin E2 (PGE2), promoting many hallmarks of cancer. Importantly, PGE2 is reported to enhance Wnt/β-catenin signalling in colorectal carcino... Read More about LGR5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2: Implications for targeting adenoma stem cells with nsaids.

EACR poster prize winner for "Autolysosomal β-catenin degradation regulates Wnt-autophagy/p62 crosstalk" (2012)
Presentation / Conference
Greenhough, A. (2012, December). EACR poster prize winner for "Autolysosomal β-catenin degradation regulates Wnt-autophagy/p62 crosstalk". Poster presented at 29th Genes & Cancer Conference, University of Warwick, Warwick, England

(EACR Poster Prize) The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both ba... Read More about EACR poster prize winner for "Autolysosomal β-catenin degradation regulates Wnt-autophagy/p62 crosstalk".

BAG-1 suppresses expression of the key regulatory cytokine transforming growth factor β (TGF-β1) in colorectal tumour cells (2012)
Journal Article
Williams, A. C., Paraskeva, C., Townsend, P. A., Hague, A., Southern, S. L., Collard, T. J., …Williams, A. C. (2013). BAG-1 suppresses expression of the key regulatory cytokine transforming growth factor β (TGF-β1) in colorectal tumour cells. Oncogene, 32(38), 4490-4499. https://doi.org/10.1038/onc.2012.480

As colorectal cancer remains the second highest cause of cancer-related deaths in much of the industrialised world, identifying novel strategies to prevent colorectal tumour development remains an important challenge. BAG-1 is a multi-functional prot... Read More about BAG-1 suppresses expression of the key regulatory cytokine transforming growth factor β (TGF-β1) in colorectal tumour cells.

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 (2012)
Journal Article
Smartt, H. J., Smartt, H., Greenhough, A., Ordóñez-Morán, P., Al-Kharusi, M., Collard, T. J., …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. British Journal of Cancer, 107(9), 1514-1517. https://doi.org/10.1038/bjc.2012.430

Background: Levels of the pro-tumorigenic prostaglandin PGE 2 are increased in colorectal cancer, previously attributed to increased synthesis through COX-2 upregulation and, more recently, to decreased catabolism. The functionally linked genes 15-pr... Read More about 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.

Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways (2012)
Journal Article
Dallosso, A., Oster, B., Greenhough, A., Thorsen, K., Curry, T., Owen, C., …Malik, K. (2012). Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways. Oncogene, 31, 4409-4419

Loss of tumor suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES) and genome-wide analyses have revealed that LRES is present in many cancer types.... Read More about Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways.

β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells (2011)
Journal Article
Huelsken, J., Smartt, H. J., Greenhough, A., Ordóñez-Morán, P., Talero, E., Cherry, C. A., …Paraskeva, C. (2012). 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. https://doi.org/10.1136/gutjnl-2011-300817

Background: Cyclooxygenase-2 (COX-2) overexpression in colorectal cancer increases levels of its protumorigenic product prostaglandin E2 (PGE2). The recently identified colorectal tumour suppressor 15-prostaglandin dehydrogenase (15-PGDH) catalyses p... Read More about β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells.

Colon tumour cells increase PGE 2 by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation (2011)
Journal Article
Williams, A. C., Moore, A. E., Smartt, H. J., Roberts, H. R., Greenhough, A., & 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. https://doi.org/10.1093/carcin/bgr210

Due to poor tumour-associated vasculature, tumour cells are subjected to a fluctuating microenvironment with periods of limited oxygen and glucose availability. Adaptive mechanisms to adverse microenvironments are important for tumour cell survival.... Read More about Colon tumour cells increase PGE 2 by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation.

The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells (2010)
Journal Article
Patsos, H. A., Greenhough, A., Hicks, D. J., Al Kharusi, M., Collard, T. J., Lane, J. D., …Williams, A. C. (2010). The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells. International Journal of Oncology, 37(1), 187-193. https://doi.org/10.3892/ijo_00000666

Despite recent advances in understanding colorectal tumour biology, there is still a need to improve the 5-year survival rate of patients with colorectal cancer as approximately 40% of patients presenting with advanced disease will remain resistant t... Read More about The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells.

The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE2 signalling in colorectal adenoma cells (2010)
Journal Article
Greenhough, A., Wallam, C. A., Hicks, D. J., Moorghen, M., Williams, A. C., & Paraskeva, C. (2010). The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE2 signalling in colorectal adenoma cells. Oncogene, 29(23), 3398-3410. https://doi.org/10.1038/onc.2010.94

Overexpression of cyclooxygenase-2 (COX-2) and elevated levels of its enzymatic product prostaglandin E2 (PGE 2) occur in the majority of colorectal cancers and have important roles in colorectal tumorigenesis. However, despite the established prosur... Read More about The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE2 signalling in colorectal adenoma cells.

HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells (2009)
Journal Article
Moore, A. E., Greenhough, A., Roberts, H. R., Hicks, D. J., Patsos, H. A., Williams, A. C., & Paraskeva, C. (2009). HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells. Carcinogenesis, 30(10), 1796-1804. https://doi.org/10.1093/carcin/bgp183

Evidence points towards a pivotal role for cyclooxygenase (COX)-2 in promoting colorectal tumorigenesis through increasing prostaglandin E2 (PGE2) levels. PGE2 signalling is closely associated with the survival, proliferation and invasion of colorect... Read More about HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells.

The COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment (2009)
Journal Article
Kaidi, A., Smartt, H. J., Greenhough, A., Moore, A. E., Roberts, H. R., Williams, A. C., & Paraskeva, C. (2009). The COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis, 30(3), 377-386. https://doi.org/10.1093/carcin/bgp014

It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E2 (PGE2) have key roles in influencing the development of colorectal cancer. Deregulation of the COX-2/PGE2 pathwa... Read More about The COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment.

The cannabinoid Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells (2007)
Journal Article
Paraskeva, C., Patsos, H. A., Williams, A. C., & Greenhough, A. (2007). The cannabinoid Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. International Journal of Cancer, 121(10), 2172-2180. https://doi.org/10.1002/ijc.22917

Deregulation of cell survival pathways and resistance to apoptosis are widely accepted to be fundamental aspects of tumorigenesis. As in many tumours, the aberrant growth and survival of colorectal tumour cells is dependent upon a small number of hig... Read More about The cannabinoid Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.

Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors (2007)
Journal Article
Huang, T. H. M., Baker, J. A., Hancock, A. L., Brown, K. W., Chilukamarri, L., Malik, S., …Malik, K. (2007). Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors. Neoplasia, 9(11), 970-978. https://doi.org/10.1593/neo.07661

Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA... Read More about Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors.

The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: A possible role for cyclooxygenase 2 (2005)
Journal Article
Patsos, H. A., Hicks, D. J., Dobson, R. R., Greenhough, A., Woodman, N., Lane, J. D., …Paraskeva, C. (2005). The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: A possible role for cyclooxygenase 2. Gut, 54(12), 1741-1750. https://doi.org/10.1136/gut.2005.073403

Background and aims: Cyclooxygenase 2 (COX-2) is upregulated in most colorectal cancers and is responsible for metabolism of the endogenous cannabinoid, anandamide, into prostaglandin-ethanolamides (PG-EAs). The aims of this study were to determine w... Read More about The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: A possible role for cyclooxygenase 2.

Cannabinoids and cancer: Potential for colorectal cancer therapy (2005)
Journal Article
Patsos, H. A., Hicks, D. J., Greenhough, A., Williams, A. C., & Paraskeva, C. (2005). Cannabinoids and cancer: Potential for colorectal cancer therapy. Biochemical Society Transactions, 33(4), 712-714. https://doi.org/10.1042/BST0330712

Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world. Therefore it is important to develop novel chemoprev... Read More about Cannabinoids and cancer: Potential for colorectal cancer therapy.

p16INK4a polymorphism: Associations with tumour progression in patients with sporadic colorectal cancer (2004)
Journal Article
McCloud, J. M., Sivakumar, R., Greenhough, A., Elder, J., Jones, P. W., Deakin, M., …Hoban, P. R. (2004). p16INK4a polymorphism: Associations with tumour progression in patients with sporadic colorectal cancer. International Journal of Oncology, 25(5), 1447-1452. https://doi.org/10.3892/ijo.25.5.1447

Deregulated tumour expression of p16INK4a has previously been described in association with clinical progression in sporadic colorectal cancer patients (CRC). Furthermore, p16INK4a promoter hypermethylation leading to gene silencing has been shown to... Read More about p16INK4a polymorphism: Associations with tumour progression in patients with sporadic colorectal cancer.