L11 Hallmarks of Cancer Flashcards
(18 cards)
definition of tumour
abnormal cell that goes through successive and inappropriate rounds of growth and division to proliferate out of control > tumour
definition of cancer
when tumour becomes malignant > cells have ability to invade surrounding tissue
most common types of cancer
carcinoma (most common): cancer arising from epithelial cells
myelomas, leukemias and lymphomas: derived from white blood cells and their precursors
sarcomas (less common): arise from connective tissue or muscle cells
difference between reductionist and heterotypic view of cancer
reductionist: view that treats cancer primarily as genetic disease caused by mutations in genes
heterotypic: view that different cell types interact differently in tumour microenvironment
neural interactions that facilitate cancer hallmarks
sustaining proliferative signalling
evading growth suppressors
activating invasion and metastasis
enabling replicative immortality
inducing angiogenesis
resisting cell death
how does sustained proliferative signalling between normal and cancer cells
normal tissues carefully control production and release of growth promoting signals > ensure homeostasis
cancer cells do not need stimulation from external signals > permanently activate signalling pathways to promote growth or destroy off switches that prevents excessive growth from these signals > cancer
difference between interaction with growth suppressors between normal and cancer cells
normal cells have tumour suppressor genes to prevent cell growth and division when not needed
cancer cells often have mutated tumour suppressor genes > over division
normal cells also have contact inhibition where they stop dividing once they fill up space; cancer cells do not have it > continue to grow and divide
what are the two barriers to stop cell proliferation
senescence: cell stops dividing forever but stays alive
crisis: if cell manage to bypass senescence, it enters a more dangerous phase where most cells die because they dividing without proper control
some cells can survive the crisis and gain ability to divide forever > immortalisation (but very rare)
what is the cause of the two barriers to stop cell proliferation
telomeres that are present at the ends of linear chromosomes > shorten with each round of division > reaches critical length > activates senescence
cancer cells have telomerase which are enzymes to keep increasing length of telomeres > will not reach critical length > keep dividing
definition of angiogenesis
process where new blood vessels form from pre-existing ones to help tumour to receive nutrients and oxygens
angiogenesis inducer: vascular endothelial growth factor A (VEGF-A)
angiogenesis inhibitor: thrombospondin-1 (TSP-1)
how is invasion and metastasis activated
local invasion > intravasation by cancer cells into nearby blood and lymphatic vessels > transit of cancer cells through lymphatic and hematogeous systems > escape of cancer cells from lumina of such vessels into parenchyma of distant tissues > formation of small nodules of cancer cells > growth of micrometastatic lesions into macroscopic tumours
how do cancer cells avoid the immune system
- reduced MHC expression > harder for immune cells like T cells to spot and attack them
- immune checkpoint proteins like PD-L1 (protein on cancer cells) bind to PD-1 on T cells > tells T cells to stop attacking > trick T cells to ignore the cancer cells
definition of metabolic reprogramming
even though glycolysis makes 18 times less ATP than oxidative phosphorylation, cancer cells still prefer it ( bc faster energy production, adaptability in low oxygen environments and glycolysis produce intermediates for growth)
to make up for efficiency, cancer cells import more glucose by increasing number of GLUT1 transporters on surfaces > brings more sugar into cell
how does inflammation contribute to cancer growth
supply bioactive molecules to tumour microenvironment: growth factors that sustain proliferative signalling, survival factors that limit cell death, proangiogenic factors, extracellular matric-modifying enzymes that facilitate angiogenesis, invasion and metastasis, and inductive signals that lead to activation of EMT
enabling characteristics of cancer
unlocking phenotypic plasticity
non mutational epigenetic reprogramming
senescent cells
polymorphic microbiomes
what is phenotypic plasticity
cancer cells’ ability to change its type or behaviour
ability usually turned off in normal cells once they become specialised
but cancer cells have this ability to evade or escape from terminal differentiation
how do cancer cells change their behaviour through non mutational epigenetic reprogramming
using EMT turned on by key gene called ZEB1 > also activates helper protein SETD1B which keeps ZEB1 active > feedback loop > locks invasive behaviour of cancer cell
what is cellular senescence
a irreversible form of proliferative arrest, evolved as a protective mechanism for maintaining tissue homeostasis > complementary mechanism to programmed cell death that serves to inactive and indue course remove diseased, dysfunctional or unnecessary cells
evokes change in cell morphology and metabolism and activation of senescence associated secretory phenotype (SASP)
induced by microenvironmental stresses like nutrient deprivation and dna damage, organelle damage etc
