Harriet R. Ferguson's research while affiliated with The University of Manchester and other places

Publications (8)

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
Full-text available
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
Full-text available
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...
Article
Full-text available
Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling...
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...
Preprint
Full-text available
Dysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in...
Article
Full-text available
Fibroblast Growth Factor (FGF) dependent signalling is frequently activated in cancer by a variety of different mechanisms. However, the downstream signal transduction pathways involved are poorly characterised. Here a quantitative differential phosphoproteomics approach, SILAC, is applied to identify FGF-regulated phosphorylation events in two tri...

Citations

... The endosomal system is notoriously hard to characterise (16), therefore our tool will be a valuable resource for distinguishing gene lists based on enrichment for different endosomal compartments. The endosomal view of SubcellulaRVis has recently been effectively utilised for visualisation of spatially resolved phosphoproteomics data describing intracellular signalling modules following dynamic cell surface receptor internalisation (28). In the future, SubcellulaRVis can be further expanded to provide more detailed views of subcompartments of, for example, the nucleus or endomembrane systems. ...
... Binding of the RAS guanine exchange factor, son of sevenless homologue 1 (SOS) and the cofactor GRB2-associated-binding protein 1 (GAB1), forms a complex that activates RAS/MEK/MAPK and RAC/JNK and PI3K/AKT signaling. All these pathways result in activation of cell proliferation, cell survival, and STAT1 and 3 activation, resulting in the induction of gene translation [29,30]. ...
... For example, an interaction between FGFR1 and EGFR can marginally increase epidermal growth factor (EGF)-mediated AKT and STAT3 signaling outputs in lung cancer cells [261]. Along this line, we have recently showed that FGFR2-IgIIIb and EGFR engage in reciprocal regulation of each other's signaling and trafficking in breast cancer cells [275], confirming that FGFR trafficking regulation may become a target for therapeutic intervention. ...
... The inhibition of lipid droplet biogenesis in poorly vascularized tumors could abolish their function as long-term lipid reservoirs and compromise the ability of cancer cells to survive prolonged periods of starvation or resume growth upon reoxygenation (Bensaad et al. 2014;Jarc et al. 2018;Pucer et al. 2013). During the final stages of revision of this manuscript, two important papers were published showing that DGAT1-mediated lipid droplet biogenesis is a relevant target for the T. Petan treatment of melanoma and glioblastoma (Cheng et al. 2020;Wilcock et al. 2020). DGAT1 was even identified as a bona fide oncoprotein that enables enhanced lipid uptake and drives melanoma formation. ...
... Notably, almost every sample (30/31) harboured a copy number loss at 10q26.12-q26.13 that includes the FGFR2 gene. Multiple studies highlight an over-expression of FGFR2 and FGFR1 in TNBC [53][54][55][56] so this was an unexpected finding. Indeed, there is currently a clinical trial for inhibition of FGFR2 (ClinicalTrials.gov ...