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BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells (2019)
Journal Article
Legge, D. N., Shephard, A. P., Collard, T. J., Greenhough, A., Chambers, A. C., Clarkson, R. W., …Williams, A. C. (2019). BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells. Disease Models and Mechanisms, 12(3), https://doi.org/10.1242/dmm.037697

To decrease bowel cancer incidence and improve survival, we need to understand the mechanisms that drive tumorigenesis. Recently B-cell lymphoma 3 (BCL-3; a key regulator of NF-κB signalling) has been recognised as an important oncogenic player in so... Read More about BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells.

Wnt signaling is a major determinant of neuroblastoma cell lineages (2019)
Journal Article
Szemes, M., Greenhough, A., & Malik, K. (2019). Wnt signaling is a major determinant of neuroblastoma cell lineages. Frontiers in Molecular Neuroscience, 12(90), https://doi.org/10.3389/fnmol.2019.00090

© 2019 Szemes, Greenhough and Malik. The neural crest (NC), which has been referred to as the fourth germ layer, comprises a multipotent cell population which will specify diverse cells and tissues, including craniofacial cartilage and bones, melanoc... Read More about Wnt signaling is a major determinant of neuroblastoma cell lineages.

LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells (2019)
Journal Article
Morgan, R. G., Ridsdale, J., Payne, M., Heesom, K. J., Wilson, M. C., Davidson, A. D., …Darley, R. L. (2019). LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells. Haematologica, 104(7), 1365-1377. https://doi.org/10.3324/haematol.2018.202846

Canonical Wnt/β-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized β-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia patients; ho... Read More about LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells.

Optimized delivery of siRNA into 3D tumor spheroid cultures in situ (2018)
Journal Article
Morgan, R. G., Chambers, A. C., Legge, D. N., Coles, S. J., Greenhough, A., & Williams, A. C. (2018). Optimized delivery of siRNA into 3D tumor spheroid cultures in situ. Scientific Reports, 8(1), https://doi.org/10.1038/s41598-018-26253-3

© 2018 The Author(s). 3D tissue culture provides a physiologically relevant and genetically tractable system for studying normal and malignant human tissues. Despite this, gene-silencing studies using siRNA has proved difficult. In this study, we hav... Read More about Optimized delivery of siRNA into 3D tumor spheroid cultures in situ.

Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis (2018)
Journal Article
Greenhough, A., Bagley, C., Heesom, K. J., Gurevich, D. B., Gay, D., Bond, M., …Williams, A. C. (2018). Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis. EMBO Molecular Medicine, 10(11), 1-13. https://doi.org/10.15252/emmm.201708699

© 2018 The Authors. Published under the terms of the CC BY 4.0 license Hypoxia is a hallmark of solid tumours and a key physiological feature distinguishing cancer from normal tissue. However, a major challenge remains in identifying tractable molecu... Read More about Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis.

Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression (2018)
Journal Article
Gurevich, D. B., Severn, C. E., Twomey, C., Greenhough, A., Cash, J., Toye, A. M., …Martin, P. (2018). Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression. EMBO Journal, 37(13), e97786. https://doi.org/10.15252/embj.201797786

© 2018 The Authors. Published under the terms of the CC BY 4.0 license Wound angiogenesis is an integral part of tissue repair and is impaired in many pathologies of healing. Here, we investigate the cellular interactions between innate immune cells... Read More about Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression.

Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma (2018)
Journal Article
Szemes, M., Greenhough, A., Melegh, Z. B., Malik, S., Yuksel, A., Catchpoole, D., …Malik, K. (2018). Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma. Neoplasia, 20(4), 335-350. https://doi.org/10.1016/j.neo.2018.01.009

© 2018 Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra- and intertu... Read More about Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma.

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity (2017)
Journal Article
Morgan, R. G., Mortensson, E., Legge, D. N., Gupta, B., Collard, T. J., Greenhough, A., & Williams, A. C. (2018). LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity. British Journal of Cancer, 118(4), 558-565. https://doi.org/10.1038/bjc.2017.412

© The Author(s) named above 2018. Background:LGR5 serves as a co-receptor for Wnt/β-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5 + cells are known to exist outside... Read More about LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity.

Genetics society prize for best talk entitled "Adaptation to hypoxia requires HIF-driven GPRC5A-YAP activity" (2017)
Presentation / Conference
Greenhough, A. (2017, July). Genetics society prize for best talk entitled "Adaptation to hypoxia requires HIF-driven GPRC5A-YAP activity". Presented at The Genetics Society 11th Mammalian Genes, Development and Disease Meeting

Selected Talk.

BACR/ECMC prize for best overall presentation, for "A new HIF target that promotes tumour cell adaptation to hypoxia" (2016)
Presentation / Conference
Greenhough, A. (2016, July). BACR/ECMC prize for best overall presentation, for "A new HIF target that promotes tumour cell adaptation to hypoxia". Presented at BACR/ECMC Conference on Therapeutic Interventions for Cancer Therapy

Selected Talk.

BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling (2016)
Journal Article
Williams, A. C., Paraskeva, C., Southern, S. L., Eagle, C. J., Collard, T. J., Urban, B. C., …Williams, A. C. (2016). BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling. Gut, 65(7), 1151-1164. https://doi.org/10.1136/gutjnl-2014-308270

Objective Colorectal cancer remains the fourth most common cause of cancer-related mortality worldwide. Here we investigate the role of nuclear factor-?B (NF-?B) co-factor B-cell CLL/lymphoma 3 (BCL-3) in promoting colorectal tumour cell survival. De... Read More about BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
Journal Article
Bagniewska-Zadworna, A., Baghdiguian, S., Baek, S. H., Baehrecke, E. H., Bae, S. H., Bae, O. N., …>100 authors, .. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222. https://doi.org/10.1080/15548627.2015.1100356

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies... Read More about Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

Circulating prostaglandins as biomarkers for colorectal cancer? (2015)
Journal Article
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?.

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.

LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma (2015)
Journal Article
Gabb, P. D., Bates, D. O., Kaidi, A., Melegh, Z., Chockalingam, S., Vieira, G. C., …Morgan, R. (2015). LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma. Oncotarget, 6(37), 40053-40067. https://doi.org/10.18632/oncotarget.5548

LGR5 is a marker of normal and cancer stem cells in various tissues where it functions as a receptor for R-spondins and increases canonical Wnt signalling amplitude. Here we report that LGR5 is also highly expressed in a subset of high grade neurobla... Read More about LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma.

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

(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
Skeen, V. R., Collard, T. J., Southern, S. L., Greenhough, A., Hague, A., Townsend, P., …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, 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.