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Comment
. 2022 Aug 9;119(32):e2210179119.
doi: 10.1073/pnas.2210179119. Epub 2022 Aug 2.

Treatment of ovarian cancer with modified anthrax toxin

Klaus Aktories  1
Affiliations
Comment

Treatment of ovarian cancer with modified anthrax toxin

Klaus Aktories. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The author declares no competing interest.

Figures

Fig. 1.
Fig. 1.
The action of the zymogen-activated anthrax toxin PAS:LF. (A, Right) The monomeric 83-kDa binding component of anthrax toxin (PA83) is activated by cleavage after the sequence RKKR by furin (the box and arrow indicate the cleavage site). In PAS, eight residues of PA in the cleavage site were changed, resulting in activation by MASPs, which are overexpressed in ovarian cancer cells. (A, Left) Monomeric PAS83 binds to anthrax receptors (ANTXR). MASPs-induced cleavage causes heptamerization of PAS63 and binding of the enzyme component, LF. At low pH of endosomes, PAS inserts into the membrane and forms a pore for translocation of LF into the cytosol. In the cytosol, LF cleaves and inactivates the kinases MEK (MAP/ERK kinase)1,2 and MKK (mitogen-activated kinase kinase) 3,4,6,7. These kinases are involved in MAP kinase pathways, which act as signal hubs to the nucleus, modulating gene expression. MAP kinase pathways are frequently activated in cancer cells. (Ras, proto-oncogene product with GTPase activity; Raf, serine/threonine-protein kinase; ERK, extracellular signal-regulated kinase; p38, p38 mitogen-activated protein kinase; JNK, c-Jun N-terminal kinase) (B) Wild-type anthrax toxin PA:LF is activated by furin, which is ubiquitously expressed. Therefore, the toxin effects are not specific. Ovarian cancer cells (red) overexpress several types of MASPs, which can activate each other. PAS:LF is mainly selectively activated by MASPs from cancer cells. Therefore, the toxic effect of PAS:LF is specific for the cancer cell.
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