10th Feb - Oncogenes and Signal Transduction Pathways in Cancer Flashcards
What are the three ways the signal can activate the receptor?
Conformational Change
Multimerization
Modification
What are the common alterations of EGFR signalling in tumours and an example of a cancer they occur in?
EGFR/ErbB1 OE in NSCL
EGFR/ErbB1 truncation of ectodomain in glioblastoma
ErbB2/HER2/Neu OE in Breast cancer
Erbb3/4 OE in Oral squamous cell carcinoma
Name a treatment that targets EGFR signalling
Herceptin targets HER20
What is the function of endothelial growth factor (EGF)?
Stimulates proliferation in many cell types
What is the function of platelet derived growth factor (PDGF)?
Stimulates proliferation in connective tissue cells
What is the function of Insulin-like growth factor (IGF-1)?
Promotes cell survival, stimulates metabolism and works with other GFs to stimulate proliferation
What is the function of transforming growth factor beta (TGF-beta)?
Regulates the effects of other GFs and regulates differentiation and embyronic development
What is the function of vascular endothelial growth factor (VEGF)?
Promotes angiogenesis and endothelial cell growth
Which cancer do mutations in Class III RTKs lead to?
Acute myeloid leukaemia (AML)
In the cytoplasm which protein is Grb2 in complex with?
Son of sevenless (Sos)
How do oncogenic mutations in Ras commonly alter its activity?
Mutants compromise the ability of GAPs to hydrolyse GTP bound by Ras –> longer Ras activation
What are guanine nucleotide dissociation inhibitors?
Proteins that bind to the GDP bound form of GTPases and prevent exchange
TUMOUR SUPPRESSORS
Outline the pathway which activates Ras
Active RTK –> Grb2 –> mSos1 -> Ras-GTP
Outline the downstream pathway from Raf
Raf –> MEK1/2 –> ERK1/2 –> Proliferation, Growth and Survival
What are the two subunits of PI3K?
Regulatory - p85
Catalytic - p110
What is the function of PI3K?
PI3K phosphorylates the 3’ position of the inositol phospholipids
What is the preferred substrate for PI3K?
PIP2
What is the role of PTEN?
Dephosphorylates 3’ position inactivating PI3K
Give an example of a cancer that PTEN is mutated in
Glioblastoma
Ovarian Cancer
Lung cancer
Melanoma
outline the PI3K signalling pathway via PKB
PI3K –> PIP3 –> PDK1 and PDK2 –> PKB –> FOXO and p27 released from nucleus –> Apoptosis, Proliferation, protein synthesis and glucose metabolism
What is FOXO?
Forkhead box proteins class O transcription factors that regulate metabolism, cellular proliferation, cell stress and possibly lifespan
What is the function of PLC-gamma?
It hydrolyses PIP2 –> DAG and IP3
What is the main downstream effect of IP3?
Releases Calcium from the ER
What is the main downstream effect of DAG release?
PKC activation
What are the physiological effects of PKC activation?
Cell Transformation
Apoptosis inhibition
Metastasis
