sustaining proliferative signalling Flashcards
how are signals transmitted in cells
through the transmembrane receptors
what are growth factors
secreted proteins and hormones that control the cells essential functions
2 ways that anti-growth factors block proliferation
forcing cells into a quiescent state (G0) and being induced to enter post-mitotic states (permanently exit cell cycle)
what is autocrine signalling
when the cancer cells produce their own growth factor signals
what is paracrine signalling
the cancer cells signal to normal cells which then respond and release growth signals for the tumour
how can tumour cells amplify signals
increasing the expression of cell surface receptors or losing regulation of the receptors
how do tumours gain independence from normal signalling
they make it look like the normal signals have been received when they haven’t
3 main stages for acquiring autonomy from growth signals
- altering external growth signals
- altering transcellular transducers of those signals
- altering intracellular circuits that translate those signals to action
what is Ras
a member of the Ras superfamily of proteins which is a family of GTPases, oncogene
what do GTPases do
bind to and hydrolyse GTP
what does Ras do
signals for a cascade in the cell permanently, no incoming growth signals needed
what cascade does RAS activate
activates the mitogen activated (MAP) kinase cascade
what else does Ras activate
PI3K/AKT/mTOR pathways
how do tumours become insensitive to anti-growth signals
hyperphosphorylated pRb sequesters and alters the function of E2F transcription factors
how is pRB inactivated
phosphorylation
what happens when pRb is inactivated
the cell cycle can progress from G1 to S
What is the gene for pRb
RB I, if both alleles are mutated then retinoblastoma occurs
what happens when pRb binds to E2F transcription factors
they are inactivated and so the cells remain in G1
what is TGFβ (transforming growth factor β)
multifunctional cytokine that binds to TGFβ receptor
what happens when TGFβ binds to its receptor
it phosphorylates itself and a signalling cascade is activated
what does TGFβ signalling cause
transcription of some genes and repression of other through Smad combinations
what cellular changes are caused by TGFβ signalling
reduction in cytostatic response
what are the 3 genes in the Myc family
c-Myc, I-Myc, n-Myc
which Myc gene is continually expressed in cancer
c-Myc, it is a proto-oncogene
