COD Cancer Flashcards
Name some changes in cellular properties that promote cancer
Resisting cell death Evading growth suppressors Sustaining proliferative signaling Inducing angiogenesis Enabling replicative immortality Activating invasion and metastasis
Normal cells require external stimulation from growth factors to promote entry into the cell cycle
How is this different from cancer cells?
They may have enhanced external stimulation eg mutations in gfr
They may have lost this dependency due to activating mutations in signal transduction components or mutations in cell cycle components
In order to maintain homeostasis, normal cells respond to inhibitory signals which regulate growth, differentiation and apoptosis
How have cancer cells lost this ability?
Loss of activity of tumour suppressor genes such as p53, PTEN & Retinoblastoma (Rb)
Aberration in developmental signalling pathways e.g. Hedgehog, Wnt and Transforming growth factor-b (TGF-b)
In order to maintain fidelity, normal cells with DNA damage are removed via apoptosis
How do cancer cells avoid apoptotic signals?
Via
Mutations that affect the intrinsic pathway of apoptosis i.e. Loss of p53 activity, upregulation of anti-apoptotic members of the BCL-2 family; down regulation of pro-apoptotic BCl-2 family members
Mutations that affect the extrinsic pathway e.g. aberrations in death receptor regulation
In normal cells & tissue, angiogenesis only occurs under very specific physiological conditions such as?
e.g. active periods of growth, female reproductive organs and wound healing.
What is the diffusion limit of oxygen through solid tissue?
200 micrometres
What is necrosis caused by?
hypoxia or lack of oxygen
True or false
Tumours require vascularisation to grow into a large mass and to prevent of necrotic cell death
True
Angiogenesis is regulated by a balance between the levels of angiogenic inducers and what?
angiogenic inhibitors
Many proangiogenic molecules are growth factors – key player is what?
vascular endothelial growth factor (VEGF)
What is VEGF expression regulated by?
hypoxia and over-activation of other growth factor signalling pathways
Normal cells shorten the ends of their chromosomes (telomeres) during every round of DNA replication which defines a finite number of cell doublings
Describe telomeres
Composed of repetitive DNA sequences (TTAGGG) and associated proteins
Protect ends of chromosomes and control chromosomal length
Shorten by 100-200 bp each DNA replication round due to limits of DNA polymerase needing an RNA primer
What is telomerase?
A form of reverse transcriptase that also contains the RNA template for the telomere repeat DNA (a)
Maintains telomere length
How do cancer cells and stem cells maintain telomere length and immortality
Produce telomerase
Cancer cells have gained the ability to invade and spread (metastasise) to distant sites by what?
Breaking cell- cell and cell –ECM attachment
Becoming more motile
Inducing angiogenesis to support ‘secondary’ tumour growth
Metastatic cells show preferential spread to particular sites - what is this known as?
organotropism
Where is the site of spread usually?
Close proximity to primary tumour
Direction of blood flow
Tumour cells get trapped in capillary bed
Distal/ non-obvious
Seed and soil hypotheses (Paget)
(cells need to match with optimum environment)
Premetastatic niche (Lynden) (distant site is prepared via circulating tumour derived fact
True or false
Less than 1:10,000 circulating tumour cells will survive to set up a secondary metastatic tumour
True
what helps mediate breakdown of cell:cell contacts and cell:ECM contact?
Src
EMT- Key regulators are transcription factors what?
SNAIL and TWIST
What are some Emerging Hallmarks and Enabling Characteristics of tumours?
Hallmarks: Avoiding immune destruction
Deregulating cellular energetics
Enabling characteristics: Tumor promoting inflammation
Genome instability and mutation
What is the rationale for cancer cells to utilise aerobic glycolysis?
Cancer cells are frequently hypoxic
Lack oxygen for oxidative phosphorylation
Process of glycolysis also generates intermediates for biosynthetic pathways such as growth