Lecture 6 - Growth Factors, Receptors and Cancer Flashcards
What is characteristic about certain signalling pathways in many cancers.
Overactive or constitutively “on” signalling pathways are found in the majority of human tumors
What are mitogens? Name two common effects they have on a cell.
Mitogens are growth factors that cause numerous cell changes including:
1 - Proliferation
2 - Migration
What are protein kinases? What is Src?
Protein Kinases can phosphorylate multiple substrate proteins (by converting ATP to ADP). Src is a posphokinase protein that is pleiotropic and has more than 50 different substrates. These subsequent substrates have a variety of roles in proliferation, angiogenesis, apoptosis, and further protein synthesis.
What is EGF-R? Why is it important?
EGF-R, or Epidermal Growth Factor Receptor, is a receptor that plays a major role in proliferation. Certain tumors have been shown to have an overexpression of this receptor. EGF-R has a protein kinase functionality.
What are RTKs? Why do we care about them?
RTKs are Tyrosine Kinase Receptors. They are important because they are involved in tumor parthenogensis (asexual replication/mitosis/meiosis)
What is the v-Erb8 oncogene?
The v-Erb8 oncogene is special because it has a truncated RTK receptor. This means that deregulation of receptor firing occurs as the receptor’s extracellular domain has been cut off (active site). This means that the receptor emits a signal (cascades/pathways) even in the ABSENCE of ligand binding.
What are the 4 methods in which deregulation of receptor firing can occur?
1 - Mutations affect structure of receptor and truncate/destroy the active site. Signals are emitted even in the absence of a ligand.
2 - Receptors can be overexpressed leading to an increase in ligands binding and signals being emitted.
3 - A conversion between paracrine (do not feed self) and autocrine (feed self) can occur. This means the receptors active site can be mutated to accept the cell’s own ligand products, a never ending positive feedback loop.
4 - ^ building off the last point, receptor active sites can also be altered to accept new ligands from other cells, and multiple types of ligands instead of the regular diet. Therefore binding and signalling increases dramatically.
What are the three ways in which overexpression of receptors can occur in a cancer cell?
1 - Increased transcription
2 - Increased translation
3 - Inhibited Destruction (old receptors)
What is a classic example of a positive autocrine signalling loop?
Kaposi’s Sarcoma = 8 different autocrine signalling loops
What can Gene Fusion result in?
Gene fusion can result in ligand independent dimerization (where both halves of an RTK receptor come together and fuse permanently) which in turn can reslut in ligand independent firing.
What are cytokine receptors? Why are they so important exactly?
Involved in the development of hematopoietic cell types. Activated following ligand binding and signal via transphosphorylation (Cup diagram)
What are notch receptors and what do they do?
Notch receptors are found mutated in many leukemias. They contribute to the Ras-mediated cell transformation
What is patched-smoothened signalling? Which types of cancer is it found to be critical in?
Signalling pathway related to proliferation and differentiation that is typically found disrupted in certain basal cell skin carcinomas.
What is canonical Wnt signalling? Give us an examples of a tumor suppressor gene that is involved in the pathway?
Beta-catenin degrades to release promoting factors or stays intact and promotes proliferation. When mutated, axin does not bind to the whole complex inhibiting beta-catenin to follow its regular routine of degrading. It can also inhibit different actions. Apc is the tumor supressor gene that is involved here.
What is non-canonical Wnt signalling? What is triggered here?
In non-canonical Wnt signalling, G protein signalling pathways can trigger cell activation.
