CE L4 Stem cells Flashcards
is it easier to target over or underactive?
over
Is any cell as likely to mutate as another?
Initially we thought this bu actually no
What is the future for cancer prognosis?
we wold get an individualised map of mutations to predict prognosis and response to therapy etc.
development of and organism relies on a balance between (3 processes)
differentiation
proliferation
apoptosis
development of and organism relies on a balance between (3 processes)
differentiation
proliferation
apoptosis
Why cant cancer cells carry out normal function?
They become undifferentiated
Why cant cancer cells carry out normal function?
They become undifferentiated
PROBLEM
Tumour masses look like they are made of many/few cell types?
Many - but cancers are clonal (arising from a single cell)
PROBLEM
Can all cancer cells recolonise?
No - only a small number can when implanted into a secondary site
PROBLEM
Cancer is a disease of proliferating cells - but…
but most mature cells don’t proliferate
PROBLEM
Cancers are caused by the accumulation of 3+ mutations - but
most cells have a finite lifetime and don’t live long enough to acquire this
4 evidences that cancer arrises from stem cells?
- Clonal
- Can recolonise
- Live long enough to get 3 mutations
- Proliferating cells
4 evidences that cancer arrises from stem cells?
- Clonal
- Can recolonise
- Live long enough to get 3 mutations
- Disease of proliferating cells
Stem cells are…
unspecified cells that reproduce themselves and/or generate more specialised cells indefinately
Specialised cells carry out a specialized function but often cannot…
divide
Changes in cell state are ………….. regulated
transcriptionally
What are progenitor cells
Unipotent e.g. haemopoetic- can only become one type of cell
What is asymmetrical stem cell
a
What is asymmetrical stem cell
Each time the cell divides it produces one daughter cell that is more differentiated and one identical.
Stem cell -> Restricted stem cell -> Progenitor cell
What are adult stem cells present for?
Healing and normal cell turnover (producing new blood cells etc.)
Problems studying adult stem cells
difficult to isolate and identify
What does recolonisation of adult stem cells suggest?
If you implant an adult stem cell in other tissues in some cases it forms a tumour. If you do this with differentiated cells the don’t
They would need to dedifferetiate first to acquire ability to proliferate.
Where are adult stem cells held?
In a stem cell niche - encapsulated environment, suppresses growth. Only allowed to proliferate to replace damaged cells.
What happens to the stem cell niche in cancer?
Cancer cell becomes independent of niche or have changes so the niche can not longer suppress them
Proliferation of adult stem cells is high so when mutations occur….
they are rapidly spread to many daughter cells
Proliferation of adult stem cells is high so when mutations occur….
they are rapidly spread to many daughter cells
Stem cells live longer giving the opportunity for
many mutations to accumulate
Many signalling pathways involved in …………………. have been shown to be mutated in cancer cells
self renewal
How do stem cells become independant on niceh
- Expasion of niche allows expansion of cancer cells
- Adaption to a different niche allowing their expanion
- Niche independance
- Shift in the programmed declined replication potential
Wnt is a …………………………… found in what cancers
protooncogene
colon
Telomeres are
repeats found at the end of chromosomes that aid chromosomal replication
Do mature cells in the body express telmerase enzymes?
no - but cancers do. It has to be reactivated, so was it never switched off if the cancer is from a stem cell?
It’s been a target for therapy as different to self
What is the function of telomeres?
Enzymes used to copy DNA need something to sit on so they don’t fall off before reaching the end
What happens to telomeres in each cell division?
Shorten - because DNA polymerase cannot copy right to the end.
What happens when the telomere is too short?
recognised as damaged DNA
p53 is activated - senescense or even apoptosis
What does measuring telomerase activity tell us about cancer?
What else do we measure with this?
Prognosis
N-myc
(high is poor)
What are telomerase enzymes?
Reverse transcriptase enzymes containing RNA template to add TTAGGG repeats onto the chromosomal ends
What is the benefit for the cancer cell of expressing telomerases?
Able to repair telomeres and so extend life
- exmples of a theoretical anti telomerase therapy
telomerase antisence
or
telomerase with mutated DNA template
- exmples of a theoretical anti telomerase therapy
telomerase antisence
or
telomerase with mutated DNA template
Patched is a
tumour supressor
Describe the patched pathway
Hh binds to patched, when bound it releases smoothened.
This releases Gli
Gli (transcription factor) - drives proliferation
2 Problems in the patched pathway that may cause cancer
Over expression oh Hh
loss of function of patched
~Describe the wnt pathway
wnt binds to frizzled .
When bound the complex draws GSK3 out of normal complex and binds to receptor.
This releases beta catenin (TF)
Drives c-myc(TF) + cyclin D expression
Drives G1 and cell cycle
How many forms of Hh are there
3 - sonic, desert and indian
What is in the normal complex with GSK3 in the Wnt pathway
APC
Axin
CKI
GSK3
Problem in Wnt pathway causing colon cancer?
loss of function of APC (so the normal complex can’t form)
WHAT IS THE ULTIMATE OUTCOME OF WNT AND Hh PAATHWAYS -
HOW DOES THIS RELATETO STEM CELLS
drives proliferation
