Introduction Flashcards
name some types of cell found in the heterogenous population of cancer which make up the tumour microenvironment
cancer cells, cancer stem cells, fibroblasts, immune cells, endothelial cells
what are the causes of cancer
genetics, lifesyle, infections, environmental exposure
what are the 6 hallmarks of cancer
evading apoptosis, sustained angiogenesis, tissue invasion and metastasis, unlimited replication, insensitivity to anti-growth signals, self efficiency in growth signals
how do cancers sustain proliferative signalling
upregulate oncogees eg Ras which is phosphorylated to form GTP bound activated Ras which activates a number of signalling cascades which affect cell division, proliferation and activation. also the MEK-ERK pathway is activated by Ras activation as this activates Raf which switches on MEK-ERK to drive proliferation
what is contact inhibition
normally when cells run out of space the stop growing
which mutation is responsible for cancer cells which do not demonstrate contact inhibition and why
NF2 gene codes for merlin which normally binds to cadherin receptors on adjacent cells when 2 cells come together causing inactivation of growth. so mutations lead to uncontrolled proliferation
what are the 2 ways of apoptotic initiation
up regulation of oncogenes and DNA damage
how can cancer cells overcome the apoptotic cascade
inactivate P53, inactivaate proapoptotic factors and upregulate apoptosis supressor proteins
how is replicative immortality achieved
telomerase is differentially expressed- at first it is switched off allowing increased DNA damage and necessary mutations can occur then it is massivley unregulated to allow for immortality
how is angiogenesis induced
Ang-2 destabilises the vessel wall of mature vessels. quiescent endothelial cells then become sensitive to VEGF causing them to proliferate and migrate to form new vessels. VEGF-A expression is regulated by Ras signalling
how does metastasis occur
primary tumours spawn pioneer cells which move out and invade adjacent tissues and travel to distant sites where space and nutrients are not limited
what are the 2 emerging hallmarks of cancer
controlling energy metabolism and immune evasion
how do cancer cells control metabolism
they use aerobic glycolysis rather than the etc
how do tumours evade the immune system
they can secrete suppressive factors e.g. TGFb
what is the paradox with regards to tumour immunosuppression
tumour microenvironment requires inflammatory immune cells to produce cytokines and chemise which are mitogenic and potentiate tumour growth, stimulate angiogenesis and induce fibroblast migration and maturation
