Jennifer Ferguson

Jennifer Ferguson
The University of Manchester · Faculty of Life Sciences

Doctor of Philosophy

About

42
Publications
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869
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Publications

Publications (42)
Article
Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells. Molecules...
Preprint
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Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibrobl...
Article
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Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine-tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains...
Preprint
Integration of signaling downstream from individual Receptor Tyrosine Kinases (RTKs) is crucial to fine tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration still r...
Article
Full-text available
Melanoma is the deadliest form of skin cancer; a primary driver of this high level of morbidity is the propensity of melanoma cells to metastasise. When malignant tumours develop distant metastatic lesions the new local tissue niche is known to impact on the biology of the cancer cells. However, little is known about how different metastatic tissue...
Article
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The BRAF‐kinase and the MAPK‐pathway are targets of current melanoma therapies. However, MAPK‐pathway inhibition results in dynamic changes of down‐stream targets that can counteract inhibitor‐action not only during treatment, but also in acquired resistant tumours. One such dynamic change involves the expression of the transcription factor MITF, a...
Article
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Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites...
Article
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Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-hi...
Article
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It is well know that cancer cells have adopted an altered metabolism and that glucose is a major source of energy for these cells. In melanoma, enhanced glucose usage is favoured through the hyper-activated MAPK pathway, which suppresses OXPHOS and stimulates glycolysis. However, it has not been addressed how glucose availability impacts on melanom...
Data
Document S1. Supplemental Experimental Procedures, Figures S1–S7, and Tables S1 and S2
Article
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Once melanomas have progressed with acquired resistance to mitogen-activated protein kinase (MAPK)-targeted therapy, mutational heterogeneity presents a major challenge. We therefore examined the therapy phase before acquired resistance had developed and discovered the melanoma survival oncogene MITF as a driver of an early non-mutational and rever...
Article
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Unlabelled: Recently, the rationale for combining targeted therapy with immunotherapy has come to light, but our understanding of the immune response during MAPK pathway inhibitor treatment is limited. We discovered that the immune microenvironment can act as a source of resistance to MAPK pathway-targeted therapy, and moreover during treatment th...
Article
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Clonal selection and transcriptional reprogramming (e.g., epithelial-mesenchymal transition or phenotype switching) are the predominant theories thought to underlie tumor progression. However, a "division of labor" leading to cooperation among tumor-cell subpopulations could be an additional catalyst of progression. Using a zebrafish-melanoma xenog...
Article
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Background The importance of the genetic background of cancer cells for the individual susceptibility to cancer treatments is increasingly apparent. In melanoma, the existence of a BRAF mutation is a main predictor for successful BRAF-targeted therapy. However, despite initial successes with these therapies, patients relapse within a year and have...
Article
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The Target Of Rapamycin TOR kinase regulates cell growth and division. Rapamycin only inhibits a subset of TOR activities. Here we show that in contrast to the mild impact of rapamycin on cell division, blocking the catalytic site of TOR with the Torin1 inhibitor completely arrests growth without cell death in S.pombe. A mutation of the Tor2 TORC1...
Article
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Background The mitogen-activated protein-kinase pathway consisting of the kinases RAF, MEK, and ERK is central to cell proliferation and survival and is deregulated in more than 90% of melanomas. MEK inhibitors are currently trialled in the clinic, but despite efficient target inhibition, cytostatic rather than cytotoxic activity limits their effic...
Article
The RAS-RAF-MEK-ERK pathway is deregulated in over 90% of malignant melanomas, and targeting MEK as a central kinase of this pathway is currently tested in clinical trials. However, dose-limiting side effects are observed, and MEK inhibitors that sufficiently reduce ERK activation in patients show a low clinical response. Apart from dose limitation...
Data
Supplemental Figure 1: MEK inhibition induces a mesenchymal shape in melanoma spheres. (a) GFP-expressing A375 cells were cultured as spheres for 3 days before they were embedded in 3D collagen. 16h later, the spheres were either treated with DMSO or with 1μM selumetinib. Images were taken at 6h. (b) Bright filed images of GFP-A375 cells treated fo...
Data
Supplemental Figure 2: SRC kinases in melanoma cells. Western blot of SRC, FYN and YES expression in primary normal melanocytes and various melanoma cell lines. ERK2 was used as loading control.
Article
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The alkyltransferase-like (ATL) proteins contain primary sequence motifs resembling those found in DNA repair O6-alkylguanine-DNA alkyltransferase proteins. However, in the putative active site of ATL proteins, a tryptophan (W83) residue replaces the cysteine at the known active site of alkyltransferases. The Escherichia coli atl gene was expressed...