L04 Cytoplasmic signalling and cancer Flashcards
What is intracellular signalling?
Set of linked biochemical events that connect a specific biological stimulus with a specific cellular response
What are the four properties of intracellular signalling pathways?
Specificity Transduce signal across membrane into cell Amplify external signal within the cell Regulate cellular signals (STAR)
What are the five layers of the signalling pathway?
Signal Receptor Transduction Intracellular targets Cellular response
=(CRITTRS)
Examples of extracellular signals?
Tastants Odorants Photons Peptides Lipids Amino acids derivatives e.g. epinephrine, histamine Nucleotides e.g. ATP Gases
=(TOPPLANG)
What is a ligand?
A molecule that binds to a specific site on another molecule, usually a receptor protein
Examples of cell signalling outcomes?
Changes in gene expression Regulate translation Regulate cell cycle Cell migration Initiate angiogenesis Initiate apoptosis
What are the three important signalling pathways in cancer?
Proliferation (mitogenesis)
Survival (anti-apoptosis)
Motility (invasion and metastasis)
=(MAIM)
What is mitogenesis?
Uncontrolled, continuous cell division leading to increased cell number and thus formation of a tumour mass
What is anti-apoptosis?
Loss of a cell’s programmed ability to commit suicide after a given number of cell divisions and/or after losing contact with its substrate
What is invasion and metastasis?
The ability of a cell to move from the primary tumour mass, into the bloodstream, or the lymph system and out again at a secondary site
Three types of mitogenic agonists?
Polypeptide growth factors
Peptides and lipids
Cytokines
Example of a polypeptide growth factor?
EGF (epithelial)
VEGF (vascular endothelial)
PDGF (platelet driven)
Three types of cell surface receptors?
Ligand gated ion channel
GPCRs
Enzyme-linked receptor e.g. GF receptor
Three steps of Growth Factor receptor signalling?
Dimerisation in extracellular space
Binding of receptor to signal
Activation of receptor
=(DEBRA)
What is Ras?
Oncogene
What does Raf recognise?
Ras-GTP
Define apoptosis.
Mechanism that allows a cell to self-destruct when stimulated by the appropriate trigger, which may result when a cell is no longer needed or becomes a threat to the organism’s health
Define anoikis.
Form of programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding ECM
Define necrosis.
Form of cell death that results from injury, disease, or other pathological state
Types of survival factors?
Mitogens
Integrins
Survival factors
What are integrins?
Cell-ECM adhesion factors
Heterdimers of alpha and beta subunits that bind to the EC, control cell survival, proliferation and cytoskeletal structure
What is the kinase that converts PIP2 to PIP3?
PI3K
What is the phosphatase that converts PIP3 to PIP2?
PTEN
What is PTEN?
Phosphatase and tumour suppressor
