Iron and Cancer

Question 1

Why is iron important in cancer?

Answer 1

RR is Fe dependent and loss –> G1/S arrest.
Essential nutrient for proliferating tumour cells.
OH
Cell cycle modulation and DNA damage sensing proteins regulated by Fe e.g. MDM2, p21, GADD45.
Haem and Fe-S cluster protein components.
TfR1 expression in most cancers.

Question 2

What could be a new haemochromatosis treatment target?

Answer 2

Knockout ZIP14 in Hfe-/- or Hfe2-/- (juvenile) –> prevention of iron accumulation in liver.

Question 3

What is HSPB1 and how is it linked to cancer?

Answer 3

Inhibits TfR1 recycling.
Knocking it down –> sensitisation of cancer cells in culture to elastin-induced ferroptosis.
HSPB1 often elevated in tumours.

Question 4

How does C-Myc increase cytosolic free iron?

Answer 4

Reduces H-ferritin, enhances TfR and IRP2, decreases Nramp1 promoter activity (pumps iron out of mphages).

Question 5

How does HIF enhance Fe uptake?

Answer 5

induces TfR1, Cp and HO-1.

HIF2 induces DCytB, DMT1 and Fpn.

Question 6

How does Fe influence Wnt signaling?

Answer 6

Promotes it.
Augments it in cells with aberrant APC or beta-catenin.
Iron loading also decreases E-cadherin expression which disrupts epithelial cell connection and frees beta catenin.

Question 7

What have studies on Caco-2 and SW480 cells shown?

Answer 7

Iron loading –> increased proliferation.
These cells have higher DCytB, Tfr, DMT-1 expression. Reduced HEPH expression and FPn moves to cytoplasm.
E-cadherin –> decreased mRNA expression and reduced promoter activity.

Question 8

What type of evidence links iron and cancer?

Answer 8

Epidemiological - Tf saturation, dietary iron and haem intake, iron overload, reduction in body stores.
Cell studies
Animal studies
Iron chelator use.

Question 9

What is the Fenton reaction and the Haber Weiss?

Answer 9

Fenton = Fe(II) + H2O2 –> Fe(III) + OH- + OH.
HW is sum of this + reduction back to Fe(II)
H2O2 + O2.- –> OH- + OH. + O2