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All Outputs (32)

5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: Implications for chemoprophylaxis in colorectal tumorigenesis (2021)
Journal Article
Dixon, S. W., Collard, T. J., Mortensson, E. M. H., Legge, D. N., Chambers, A. C., Greenhough, A., …Williams, A. C. (2021). 5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: Implications for chemoprophylaxis in colorectal tumorigenesis. British Journal of Cancer, 124, 1959–1969. https://doi.org/10.1038/s41416-021-01354-5

Background: Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing i... Read More about 5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: Implications for chemoprophylaxis in colorectal tumorigenesis.

Transcriptomic analyses of MYCN-regulated genes in anaplastic Wilms' tumour cell lines reveals oncogenic pathways and potential therapeutic vulnerabilities (2021)
Journal Article
Szemes, M., Melegh, Z., Bellamy, J., Park, J. H., Chen, B., Greenhough, A., …Malik, K. (2021). Transcriptomic analyses of MYCN-regulated genes in anaplastic Wilms' tumour cell lines reveals oncogenic pathways and potential therapeutic vulnerabilities. Cancers, 13(4), Article 656. https://doi.org/10.3390/cancers13040656

The MYCN proto-oncogene is deregulated in many cancers, most notably in neuroblastoma, where MYCN gene amplification identifies a clinical subset with very poor prognosis. Gene expression and DNA analyses have also demonstrated overexpression of MYCN... Read More about Transcriptomic analyses of MYCN-regulated genes in anaplastic Wilms' tumour cell lines reveals oncogenic pathways and potential therapeutic vulnerabilities.

A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer (2020)
Journal Article
Nounu, A., Greenhough, A., Heesom, K. J., Richmond, R. C., Zheng, J., Weinstein, S. J., …Relton, C. L. (2021). A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer. Cancer Epidemiology, Biomarkers and Prevention, 30(3), 564-575. https://doi.org/10.1158/1055-9965.EPI-20-1176

Background: Evidence for aspirin’s chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new... Read More about A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer.

A Wnt-BMP4 signaling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma (2020)
Journal Article
Szemes, M., Melegh, Z., Bellamy, J., Greenhough, A., Kollareddy, M., Catchpoole, D., & Malik, K. (2020). A Wnt-BMP4 signaling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma. Cells, 9(3), Article 783. https://doi.org/10.3390/cells9030783

The Wnt and bone morphogenetic protein (BMP) signaling pathways are known to be crucial in the development of neural crest lineages, including the sympathetic nervous system. Surprisingly, their role in paediatric neuroblastoma, the prototypic tumor... Read More about A Wnt-BMP4 signaling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma.

BCL–3 promotes cyclooxygenase–2/prostaglandin E2 signalling in colorectal cancer (2020)
Journal Article
Collard, T. J., Fallatah, H. M., Greenhough, A., Paraskeva, C., & Williams, A. C. (2020). BCL–3 promotes cyclooxygenase–2/prostaglandin E2 signalling in colorectal cancer. International Journal of Oncology, 56(5), 1304-1313. https://doi.org/10.3892/ijo.2020.5013

First discovered as an oncogene in leukaemia, recent reports highlight an emerging role for the proto-oncogene BCL-3 in solid tumours. Importantly, BCL-3 expression is upregulated in >30% of colorectal cancer cases and is reported to be associated wi... Read More about BCL–3 promotes cyclooxygenase–2/prostaglandin E2 signalling in colorectal cancer.

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), Article dmm037697. 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.

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), Article e8699. 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), Article 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.

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, Article 7952. 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.

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.

LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma (2015)
Journal Article
Vieira, G. C., Chockalingam, S., Melegh, Z., Greenhough, A., Malik, S., Szemes, M., …Malik, K. (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.

BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling (2015)
Journal Article
Urban, B. C., Collard, T. J., Eagle, C. J., Southern, S. L., Greenhough, A., Hamdollah-Zadeh, M., …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.

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.

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.

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.