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CAN Sem 4 > L04 Cytoplasmic signalling and cancer > Flashcards

L04 Cytoplasmic signalling and cancer Flashcards

1
Q

What is intracellular signalling?

A

Set of linked biochemical events that connect a specific biological stimulus with a specific cellular response

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2
Q

What are the four properties of intracellular signalling pathways?

A 
Specificity
Transduce signal across membrane into cell
Amplify external signal within the cell
Regulate cellular signals 
(STAR)
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3
Q

What are the five layers of the signalling pathway?

A 
Signal
Receptor
Transduction
Intracellular targets
Cellular response

=(CRITTRS)

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4
Q

Examples of extracellular signals?

A 
Tastants
Odorants
Photons
Peptides
Lipids
Amino acids derivatives e.g. epinephrine, histamine
Nucleotides e.g. ATP
Gases

=(TOPPLANG)

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5
Q

What is a ligand?

A

A molecule that binds to a specific site on another molecule, usually a receptor protein

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6
Q

Examples of cell signalling outcomes?

A 
Changes in gene expression
Regulate translation
Regulate cell cycle
Cell migration
Initiate angiogenesis
Initiate apoptosis
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7
Q

What are the three important signalling pathways in cancer?

A

Proliferation (mitogenesis)
Survival (anti-apoptosis)
Motility (invasion and metastasis)

=(MAIM)

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8
Q

What is mitogenesis?

A

Uncontrolled, continuous cell division leading to increased cell number and thus formation of a tumour mass

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9
Q

What is anti-apoptosis?

A

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

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10
Q

What is invasion and metastasis?

A

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

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11
Q

Three types of mitogenic agonists?

A

Polypeptide growth factors
Peptides and lipids
Cytokines

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12
Q

Example of a polypeptide growth factor?

A

EGF (epithelial)
VEGF (vascular endothelial)
PDGF (platelet driven)

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13
Q

Three types of cell surface receptors?

A

Ligand gated ion channel
GPCRs
Enzyme-linked receptor e.g. GF receptor

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14
Q

Three steps of Growth Factor receptor signalling?

A

Dimerisation in extracellular space
Binding of receptor to signal
Activation of receptor

=(DEBRA)

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15
Q

What is Ras?

A

Oncogene

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16
Q

What does Raf recognise?

A

Ras-GTP

17
Q

Define apoptosis.

A

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

18
Q

Define anoikis.

A

Form of programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding ECM

19
Q

Define necrosis.

A

Form of cell death that results from injury, disease, or other pathological state

20
Q

Types of survival factors?

A

Mitogens
Integrins
Survival factors

21
Q

What are integrins?

A

Cell-ECM adhesion factors
Heterdimers of alpha and beta subunits that bind to the EC, control cell survival, proliferation and cytoskeletal structure

22
Q

What is the kinase that converts PIP2 to PIP3?

A

PI3K

23
Q

What is the phosphatase that converts PIP3 to PIP2?

A

PTEN

24
Q

What is PTEN?

A

Phosphatase and tumour suppressor

25
Q

What goes wrong to initiate cancer development?

A

Protein mutation (activating)
Protein mutation (inactivating/deleting)
Protein addition
Protein amplification

26
Q

How are signals transduced from one protein to another signalling pathway?

A

Generation of intracellular signals

27
Q

Types of intracellular signals?

A 
Sugars
Ions
Gases
Nucleotides
Lipids

=(SIGNL)

28
Q

What is required of second messengers?

A

Rapidly generated, diffusable, and removed

29
Q

What is changed to generate intracellular signals?

A

Localisation of a component
Enzyme Activity of protein
Concentration of an intracellular ligand

=(LEAC)

30
Q

When EGF binds to EGFR, what happens to Grb2?

A

Grb2 gets phosphorylated, which activates SOS to convert Ras-GDP to Ras-GTP, which in turn is recognised by Raf protein and proliferation ensues

31
Q

What type of receptor is EGFR?

A

Receptor tyrosine kinase

32
Q

Significance of HER2?

A

Overexpression leads to constitutive signalling

HER2 positive breast cancer shortens survival

33
Q

What is Herceptin?

A

Humanized anti-HER2 antibody; high affinity and specificity

34
Q

What is Imatinib (/Gleevec)?

A

Abl-specific tyrosine kinase inhibitor; it blocks the ATP binding site of Abl kinase. Has broad spectrum anti-proliferative activity against haematological and solid tumour cell lines

35
Q

Side fx of Imatinib?

A

Hepatic toxicity

Neutropenia at high doses

36
Q

How might there be resistance to Imatinib?

A

Mutations in kinase domain
Amplification of BCR-Abl fusion gene
Multidrug resistance

CAN Sem 4 (6 decks)

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