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Acta Physiologica 2009; Volume 195, Supplement 667
XXXV Congress of The Spanish Society for Physiological Sciences
2/17/2009-2/20/2009
Valencia, Spain
THE ROLE OF KV10.1 (EAG1) IN TUMOR BIOLOGY
Abstract number: S28
Pardo1 LA, Sanchez1 A, Downie1 B, Napp1 J, Hartung1 F, Alves1 F, Stuhmer1 W
1Max-Planck Institute of Experimental Medicine Hermann-Rein-Str. 3, 37075 Gttingen, Germany
Aim:
Ether-á-go-go-1 (Eag1, Kv10.1) is a CNS-localized voltage-gated potassium channel that is found ectopically expressed in a majority of extra-cranial solid tumors and a significant fraction of leukemias. Its specificity for tumor tissue makes it an attractive target for "theranostic" approaches to tumor management.
Methods:
We will present strategies based on antibody engineering to take advantage of the unique distribution and properties of Eag1. Although the implication of Eagi1 n tumor biology seems clear, the mechanisms by which the channel contributes to tumor progression remain elusive. In vivo and in vitro techniques identify a candidate mechanism, which surprisingly is independent of permeation.
Results:
Our data suggest that Eag1 interferes with the cellular mechanism for maintaining oxygen homeostasis, increasing HIF-1 activity, and thereby VEGF secretion and tumor vascularization and that this interference occurs by direct interaction between members of the HIF pathway and parts of the channel. Increased resistance to hypoxic environment can explain a selective advantage conferred to the cells expressing the channel and thereby its high frequency of expressing in tumors.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 667 :S28