CANCER TRAITS 3 Flashcards
What is the aerobic cell metabolism
- glucose is turned into pyruvate (via glycolysis) in cytosol, then turned into CO2 via oxidative phosphorylation in the mitochondria
- uses -36 mol ATP/mol glucose
what is the anaerobic cell metabolism
- glucose to pyruvate via glycolysis then pyruvate is turned into lactate via fermentation
- uses 2 mol ATP/mol glucose
What is cancer cell metabolism
when cancer cells adjust energy metabolism to fuel cell growth and division
what is cancer cell metabolism called
aerobic glycolysis or the warburg effect
- even in oxygen presence, energy metabolism is limited to glycolysis and lactate production
How do cancer cells reprogramme their metabolism
- Glucose transporters
- activation oncogenes (e.g. Ras, Myc)
- mutation of tumour suppressors
-Reliance on glycolysis is more noticeable under hypoxia–> upregulates GLUTs & other enzymes - This reprogramming seems counterintuitive; cancer cells must compensate for lower ATP production
- Glycolisis intermediates used for biosynthesis of macromolecules (e.g. amino acids) & organelles required for assembling new cells
so what do cancerous cells do instead of producing more energy?
they produce metabolites that can be reused (recycling process) - therefore creating the building blocks of producing new cells and they get that by changing their metabolism by lactate fermentation
How are mutations rare in normal cells?
DNA sequences remain intact & mutations are rare due to:
Genome maintenance systems & repair enzymes; detect & fix DNA
DNA monitoring; monitor genomic integrity & force damaged cells into senescence or apoptosis
Multiple mutations are unlikely to occur within human life span
How does cancer cells increase mutation traits?
by compromising:
Components of genomic maintenance system–> increasing sensitivity to mutagenic agents
Surveillance systems
yet cancers are frequent: genomes of tumour cells acquire increased mutability
What are genome caretakers
Defects of DNA maintenance system (caretakers of the genome) can affects genes involved in:
Detecting DNA damage & activating repair machinery
Directly repairing damaged DNA
Inactivating mutagenic molecules before DNA damage occurs
Assuring correct chromosomal segregation during mitosis
what are example of ‘caretakers’
-P53 tumour suppressor: in response to DNA damage–> cell cycle arrest to allow DNA repair or apoptosis
-Telomerase: loss of telomeric DNA–> genome instability & chromosomal abnormalities
- Apoptosis: apoptotic body DNA can be incorporated into neighbouring cells–> genetic diversity of tumour cell types
What genomic instability
Genomic instability is intrinsic to human cancer cells
Large number of genome maintenance & repair defects
Defects in genome maintenance & repair are advantageous for tumour progression
Accelerate rate at which precancer cells accumulate favourable genotypes
How do tumours promote inflammation?
infiltrated with innate & adaptive immune cells causing inflammation
what are the genes involved in that the defects of DNA maintenance system has affected?
Detecting DNA damage & activating repair machinery
Directly repairing damaged DNA
Inactivating mutagenic molecules before DNA damage occurs
Assuring correct chromosomal segregation during mitosis
what is paradoxically?
tumour associated inflammation enhance tumorigenesis & cancer progression
What are the tumour promoting inflammatory cells?
Macrophages
Mast cells
Neutrophils
T & B lymphocytes
Inflammation supplies bioactive molecules to tumours, what are the examples?
- Growth factors (EGF)–> sustain proliferative signalling
- Survival factors–> limit cells death
- Pro-angiogenic factors (cytokines)
- Extracellular, matrix-modifying enzymes (MMPs)–> facilitate angiogenesis, invasion & metastasis
- Inductive signals–> activate EMT
What is immune surveillance?
Immune system (innate & adaptive cells) monitors cells & tissues
Recognises & eliminates developing tumours
How do cancer cells evade immune surveillance?
- Disrupting CTLs (cytotoxic T lymphocytes) & NK (natural killer cells) through secretion of immunosuppressive factors (TGF-beta)
- Recruiting immunosuppressive inflammatory cells (Tregs, MDSCs)
3.Interfering with antigen presentation by downregulating parts of antigen processing machinery or antigen expression–> CTLs no longer recognise tumour antigens
4.Tolerance & immune deviation:
Don’t express co-stimulatory molecules–> anergy or tolerance in T cells
Change T cell subtypes
Express inhibitory molecules like programmed death ligand (PD-L1)
what are tregs?
regulatory T cells
How do solid tumours do?
or limit immunological killing–> avoid eradication
what are MDSCs?
myeloid derived suppressor cells
what do progenitor cells do?
differentiate into specialist cell types (terminal differentiation) or continue to replicate (self renewal)
How can cancer cells change differentiation state?
Dedifferentiated back to progenitor states
Remain partially differentiated
Change differentiation pathway (transdifferentiation)
what are epigenetic changes?
genome changes without alterations in DNA sequence
changes in gene activity and expression produced by DNA methylation and histone modification
epigenetic reprogramming in cancer can affect tumour heterogeneity and microenvironement
