Cancer Cell Signalling (Tumbarello) Flashcards
`
How do cells make decisions?
Using cell signalling
Cells must continually sense and respond to environmental cues
- Metabolites, hormones, presence of other cells, pathogens…
- Cells perceive their state and adapt using signalling
- Cells make important decisions based upon their surroundings e.g. proliferate or die
Why do we study cell signalling in cancer cells
Cell signaling is altered in most cancers
- Signaling turned on and unresponsive to inhibition
- Volume of signaling increased
- Signaling at wrong time or place
Alterations of cell signaling enable the cell to evade normal regulatory controls
What are oncogenes and tumour supressors?
Oncogenes
- Capable of cellular transformation leading to cancer
- Derived from proto-oncogenes (in normal cells) typically through mutation or over-production
- Encode oncoproteins, typically function as receptors or other components of cell signalling pathways
Tumour suppressors
- Suppresses or controls proliferation
- Mutations lead to loss of function (typically recessive), removal of inhibition
- Encode proteins with diverse functions in regulation of cell cycle, apoptosis, signaling
What do many drugs target, and give examples
Singalling molecules
- New targeted therapies mostly directed against signalling proteins e.g. kinases
- Monoclonal antibodies that inhibit growth factor receptor (e.g. Herceptin in breast cancer)
- Tyrosine kinase inhibitors (e.g. Imatinib [Gleevec] in chronic myelogenous leukaemia –targeting BCR-Abl)
Why is it important to research cell siganlling for cancer?
Signalling is fundamental to many areas of biology
Many oncogenes encode mutated forms of signalling processes
Studying oncogenes has enabled understanding process of signalling
Is there evolutionary conservation of signalling?
Pathways are conserved across animal evolution
Model systems can be used to study cancer signaling pathways
Many cancer signaling pathways are important regulators during embryogenesis and development
- e.g. Wnt, Notch, Hedgehog, TGF-Beta
What is cell signalling and signal transduction?
- Cell signaling
The mechanisms that cells use to perceive and adapt to their state and surroundings - Signal transduction
The biochemical process that facilitates information processing by the cell
What are some information processing challenges?
Transmission through impermeable barrier (plasma membrane)
Specificity of response
Signal amplification
Feedback of outputs to inputs
Coordination and integration of multiple signals
How do cell signalling pathways work?
Cellular signaling involves a cascade of proteins that undergo state changes (e.g., phosphorylation, conformational switches) to transmit information
Nodes within pathways act as integration hubs, summing multiple inputs (positive and negative regulators) to produce an output.
These nodes are influenced by various environmental ligands and pathways, maintaining a finely tuned balance to prevent dysregulation.
What are some key signalling pathways in cancer?
Ras and Wnt signalling pathways
Disruption in key pathways can disturb cellular balance, driving processes like gene expression changes, cell cycle dysregulation, and cancer progression.
How is information transmitted through
pathways?
Proteins in signaling pathways act as switches, altering states (e.g., via phosphorylation, GTP binding, or ligand-receptor interactions) to regulate responses
Phosphorylation doesn’t always activate proteins—it may also inactivate them, highlighting the importance of context.
Ligands can trigger signaling through binding and dissociation events, be internalized for signal termination, or target specific cellular locations (e.g., membranes, nucleus).
How is protein state modified?
Post-translational modifications alter protein state via:
- Writers e.g. kinases
- Erasers e.g. phosphatases
What are the 2 main areas for singalling pathways?
- Plasma membrane / cytoplasmic events
- Nuclear events and gene-expression
Processes operate at different scales
Feedback is essential (gene-expression targets may be feedback
regulators of pathway)
