Cell Signalling Pathways

Question 1

How do cells comminucate with each other?

Answer 1

Electrical: very fast and depends upon the presence of gap junctions to allow information to be passed directly from one cell to its neighbour

Chemical: major form of information transfer between cells. One cell releases a chemical stimulus which alters activity of target cells. Target cells have receptors capable of detecting incoming signals and transferring info to the appropriate internal cell signalling pathway to bring about a change in cellular activity

Question 2

How is a signalling pathway developed?

Answer 2

In order to trigger a response, the signals must cross the cell membrane

• most signals bind to a receptor protein, causing a change in shape thereby passing information into the cell
• signals most often move through the cell by passing from protein to protein, each protein modifying the next –> signalling pathway

Question 3

Give some examples of signalling molecules:

Answer 3

• growth factors - EGF, TGFa, TGFb, FGF
• hormones - insulin, cortisol
• extracellular matrix molecules - fibronectin, laminin
• drugs
• chemicals

Question 4

What are the classes of transmembrane receptors for water soluble chemicals?

How does signalling occur by phosphorylation?

Define phosphorylation and dephosphorylation:

Answer 4

• ligand-gated ion channels
• G protein coupled receptor (GPCR)
• enzyme linked receptors
• intracellular receptors

Signalling by phosphorylation:

Signal –> kinase 1 –> kinase 2 –> kinase 3 –> target –> effect

Phosphorylation: the chemical addition of a phosphoryl group to an organic molecule which is carried out by kinases

Dephosphorylation: removal of a phosphoryl group carried out by the enzyme group phosphatases

Question 5

What are the 5 key signalling based mechanisms that can happen in any disease process?

Answer 5

• losing the signal e.g. type I DM
• when a signal doesn’t reach its target e.g. MS
• when the target ignores the signal e.g. T2DM
• too much signal e.g. brain damage by excitotoxicity
• multiple breakdowns e.g. cancer

Question 6

How can cancer form and develop into large tumours?

Answer 6

Cancer begins when a cell gains the ability to grow and divide

• this unregulated growth triggers a signal for self destruction
• when the cell also loses the ability to respond to death signals, it divides out of control, forming a tumour
• later cell communication events cause blood vessels to grow into the tumour, enabling it to grow larger
• additional signals allow the cancer to spread to other parts of the body

Question 7

What are the hallmarks of cancer?

Answer 7

Collection of 6 characteristics:

• sustaining proliferative signalling
• evading growth suppressors
• activating invasion and metastases
• enabling replicative immortality
• inducing angiogenesis
• resisting cell death

Question 8

What is oral cancer?

What is the most common type of oral cancer?

What are some risk factors?

Answer 8

Oral cancer: a subgroup of head and neck malignancies that develop at the lips, tongue, salivary glands, gingivae, FOM, oropharynx, buccal surfaces and other intra-oral locations

• majority of oral cancers are squamous cell carcinomas (OSCC)

Risk Factors:

• alcohol, tobacco use, viruses (HPV, EBV), occupational exposure, UV

Question 9

List some growth factors in OSCC:

Answer 9

Epidermal growth factor (EGF) and TGFa

• promotes cell proliferation in oral tissues
• overexpressed in oral carcinomas
• stimulates target cells by binding to the EGFR

TGFb - associated with more aggressive disease and worse survival

FGF - fibroblast growth factor

• FGF signals are engaged in various hallmarks of cancer

VEGF family

• plays an important role in angiogenesis