Cell Death

Key Knowledge:

Disruption to the regulation of the cell cycle and malfunctions in apoptosis that may result in deviant cell behaviour: cancer and the characteristics of cancer cells

Cells have a limited proliferative capacity, after which the cell enters an ageing phase (senescence) which leads to cell death

Cell death can be either uncontrolled (necrosis) or programmed and regulated (apoptosis)

Necrosis is the premature death of a cell, caused by disruption to the cell by injury, toxins or nutritional deprivation

The cell loses functional control and the plasma membrane destabilises, causing the cell to swell and eventually burst
The uncontrolled release of cell contents causes inflammation, which potentially damages the surrounding tissues

Apoptosis is programmed cell death and is regulated by molecular signals which inhibit or promote this process

The cytoskeleton breaks down, causing the cell to shrink and the plasma membrane to form bulges (blebbing)
The cell contents are repackaged within these blebs, which fragment into apoptotic bodies for recycling by other cells

Apoptosis

Apoptosis can be triggered by signals initiating within the cell (intrinsic pathway) or via external signals (extrinsic pathway)

Both pathways trigger the activation of caspases, which cleave specific proteins in the cytoplasm and nucleus

In the intrinsic pathway, the mitochondrial membrane becomes more permeable and releases pro-apoptotic proteins

This pathway is initiated by internal signals (e.g. DNA damage) and the pro-apoptotic proteins activate caspases

In the extrinsic pathway, death receptors on the cell surface become activated and initiate a pro-apoptotic signalling cascade

This pathway is initiated by external ligands (e.g. cytokines) and the signalling cascade will trigger caspase synthesis

Apoptosis is a natural and necessary part of organismal growth and development, and is involved in a variety of processes:

The development of fingers and toes in the foetus (as a result of the controlled loss of tissue between them)
The loss of endometrial tissue during menstruation occurs via the loss of cells forming part of the uterine lining
The removal of excess plasma cells after a successful immune response occurs due to apoptosis
Certain infected or cancerous cells may be destroyed via apoptosis

Cancer

Cancer is a disease caused by uncontrolled cell division and results in the formation of abnormal cell growths (called tumours)

Tumour cells may either remain in their original location (benign) or spread and invade neighbouring tissues (malignant)
The spread of a tumour from one location (primary tumour) to another location (secondary tumour) is called metastasis
Secondary tumours are defined according to the origin of the primary tumour (e.g. secondary breast cancer of the liver)

In order for tumours to grow, the cancer cells release molecular signals to promote local vascularisation (i.e. new blood vessels)

This increase in blood supply via angiogenesis provides the tumours with the nutrients they need to grow and potentially spread

Carcinogens

Cancers are caused by mutations to genes that promote division (proto-oncogenes) or trigger apoptosis (tumour suppressor genes)

Mutagenic agents that specifically trigger cancer-causing mutations are collectively described as carcinogens

Proto-oncogenes code for proteins (such as cyclins) which promote progression through the eukaryotic cell cycle

When a proto-oncogene becomes mutated, it is converted into an oncogene that no longer regulates cell cycle progression
In essence, oncogenes cause cancer by de-regulating the cell cycle, so that the rate of cell division is permanently increased

Tumour suppressor genes code for proteins that repress progression through the eukaryotic cell cycle or promote apoptosis

When a tumour suppressor gene becomes mutated, the cell can no longer undergo programmed death and will divide uncontrollably
Because tumour suppressor genes normally function to prevent cancer development, they are also referred to as anti-oncogenes

Cancer Cells

Cancer cells can commonly avoid immune detection as they are not foreign bodies but abnormally functioning body cells

This makes them difficult to treat – common strategies involve surgical removal and chemotherapy
However there are differences between normal and cancerous tissues which may allow for future therapies

Brent Cornell