Lecture 25 - Cancer Flashcards

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1
Q

name 4 mechanisms by which tumour cells contribute e-cadherin loss

A
  1. degredation by mmp3 protease
  2. suppression of e cadherin synthesis
  3. enchanced e-cadherin ubiquitination by tyrosine
  4. phosphorylation via c-src kinase action
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2
Q

to what motif to integrin receptors bind to?

A

RGD motifs, arg, gly, asp

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3
Q

what kind of dimer is integrin and what is their affinity for one another?

A

it is a heterodimer of alpha and beta chains, their affinities are low, allowing for a dynamic interaction

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4
Q

true or false

erbB2 receptor has no ligand, yet somehow continues to signal?

A

true

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5
Q

which receptor does herceptin target?

A

erbB2

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6
Q

what kind of dimer(s) can the erbB receptors form, and what occurs as a result?

A

they can form both homo and heterodimersthis activates their cytosolic domain, which has a tyrosine kinase. this results in reciprocal phosphorylation of their cytoplasmic tails (transphosphorylation)

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7
Q

what is the benefit of erbB receptors being able to form dimers and why is its overexpression beneficial to tumour cells?

A

it allows a limited number of ligands to activate many receptors

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8
Q

describe how a tumour cell can utilise an autocrine pathway to benefit further from overexpressed erbB receptors

A

by producing even more ligands that can already act on many receptors, the cell growth signal is amplified greatly

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9
Q

how can erbB receptors be turned off?

A

dephosphorylating their cytoplasmic tails

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10
Q

what happens when an extracellular domain is missing in erbB receptors, and does this mutation occur in humans?

A

the receptor is constitutively active. fortunately, this doesnt occur in humans

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11
Q

where at the cytoplasmic tails does tyrosine kinase phosphorylate?

A

it phosphorylates the many tyrosine residues found along the cytoplasmic tail

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12
Q

describe how PIs can act as second messengers, and describe what feature allows many diverse roles

A

the inositol unit of the PI can be phosphorylated at different carbons. This is highly specific and typically requires its own enzyme to do so. This allows it to act as a second messenger with high capability for diverse roles

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13
Q

to what domain of EGFR does phospholipase gamma bind to, and what occurs when it does?

A

SH2 domain. upon binding, PLC gamma is phosphorylated by EGF receptor kinase.

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14
Q

what is the function of an active PLC gamma?

A

it cleaves off the inositol unit to result in a diacyl chain and free inositol

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15
Q

what is the function of a diacyl chain following cleavage of its inositol unit?

A

typically activates protein kinase C which promotes cell growth

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16
Q

what is the function of a free inositol (IP3 specifically) following diacyl cleavage?

A

typically acts on the ER to mobilise Ca2+

17
Q

Describe the function of PI3 kinase

A

it binds to an autophosphorylated EGF receptor, phosphorylating PI4,5BP to PI3,4,5TP, which can dock onto two protein kinases to activate them. When activated, they will promote cell growth