Growth factor signalling and cancer

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Characteristics of cancer cell
Immortal, no contact inhibition, metastasise, dedifferentiated, loss of genetic ability to stop division
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Growth factor definition
Naturally occurring polypeptide that stimulates growth, differentiation, migration and cell division
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Growth factors bind and activate
Receptor tyrosine kinases (RTKS)
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EGFR stands for
Epidermal Growth factor receptor
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FGFR stands for
Fibroblast Growth factor receptor
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Describe general activation of RTKs
Lecture 5, page 2 slide 2
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What mechanisms of RTK over-activation lead to oncogenic transforation
Chromosomal translocation, gene amplification, impaired degradation and gain of function mutation
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The Philadelphia chromosome forms as a result of
Translocation between chrom 9 (ABL gene) and chrom 22 (BCR)
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How does Gleevec work
Binds ATP binding site on RTK, ATP can no longer bind and activate the RTK domain. Signalling cascade is stopped
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Name an EGFR orphan receptor
HER2
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Which EGFR family members form heterodimers?
HER2 and EGFR
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How does HER2 prevent endocytosis
Forms heterodimer with EGFR
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How does binding of EGF cause EGFR dimerisation?
Relieving autoinhibition
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What four signalling cascades are involved in EGFR signalling?
Ras/MAP-K, STATs, PLC-gamma and PI3K/Akt
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Name an oncoproteins in the Ras/MAPK pathways and their effect
Ras or Raf or Ap-1 / Cell proliferation, increase cell survival and migration
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Although signalling can seize through ligand-induced endocytosis of EGFR, what can still drive signalling?
Receptors endocytosed which are are signally from the endosomes
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Name a a type of cancer EGFR over-expression can be seen in
Mammary carcinomas or Oral carcinomas or Head and neck cancer
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EGFR therapeutic targets
Herceptin, Erbitux, Pentacyclic triterpenes
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How is FGFR activated
Lecture 5, page 5, slide 4
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______ terminates FGFR signalling
Endocytosis
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The possible mechanism for deregulated FGF signalling are
Activating mutations, overexpression of receptor, autocrine or paracrine secretion of FGF
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FGFR therapeutic targets
FGF8 and Masitinib
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Growth factor definition

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Naturally occurring polypeptide that stimulates growth, differentiation, migration and cell division

Card 3

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Growth factors bind and activate

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Card 4

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EGFR stands for

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Card 5

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FGFR stands for

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