carcinogenesis 3: limitations on normal tissues Flashcards
what is density-dependence of cell division?
cells in a confluent monolayer (ie high density) cease proliferating and slow down many other metabolic activities due to competition for external growth factosr
what is anchorage dependence?
cells require to be binding to ECM in order to respond properly to soluble growth factors
what is the mechanism of anchorage dependence?
growth factor receptors & integrin signalling complexes can each activate identical signallling pathways (eg MAPK)
- individually activation is weak &/ transient
- together activation is strong & sustained ie separate signalling pathways act synergistically
what interactions happen short term between cells:
transient interactions between cells which do not form cell-cell junctions
what interactions happen long term between cells?
stable interactions -> cell-cell junctions
what is contact inhibition of locomotion?
when most non-epithelial cells collide they do not form stable cell-cell contacts
- actually repel each other by paralysing motility at contact site -> promotes formation of motile site at another site of cell -> moves off in opposite direction
what is contact inhibition of growth?
cell-cell junctions inactivate MAPK so that cells already surrounded by others do not proliferate much
what are the types of cell junctions?
tight junctions
adherens (linked to actin)
desmosomes (linked to intermediate filaments)
gap junctions
hemidesmosomes (cell-ECM - linked to intermediate filament)
what is contact-inducing spreading?
contact between epithelial cells -> mutual induction of spreading
what happens when a cell is not in contact with another cell?
no cell-cell junctions -> activated MAPK -> decreased p27kip -> high proliferation
what is the product of the APC-gene?
protein involved in degradation of βcatenin
what is the mechanism for contact inhibition of proliferation?
when bound to cadherin at membrane, βcatenin levels degraded quickly so βcatenin-LEF1 complex doesn’t act
what happens if the cell is not in contact with other cells?
βcatenin levels rise (as a result of inhibition of degradation or loss of cadherin-mediated association) ->
β-catenin-LEF1 complex enters nucleus ->
upregulates gene expression ->
cell proliferation
what other adhesion-associated signalling pathways affect CIIP?
clustering of cadherins after cell-cell contact alters activation of small gtpases (eg RAC activated RHO inhibited) -> influences proliferation
- also some growth factors are associated with cell-cell junctions
what happens when cells lose their social skills?
proliferate uncontrollably (lose density dependence of proliferation)
- are less adherent & will multilayer (lose contact inhibition of locomotion and anchorage dependence)
- epithelia break down cell-cell contacts
