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XB-ART-38824
Proc Natl Acad Sci U S A October 28, 2008; 105 (43): 16608-13.

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells.



Abstract
Ion transporters, and the resulting voltage gradients and electric fields, have been implicated in embryonic development and regeneration. These biophysical signals are key physiological aspects of the microenvironment that epigenetically regulate stem and tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, a potassium channel known to be involved in human Romano-Ward and Jervell-Lange-Nielsen syndromes when mutated. Misexpression of its modulatory wild-type beta-subunit XKCNE1 in the Xenopus embryo resulted in a striking alteration of the behavior of one type of embryonic stem cell: the pigment cell lineage of the neural crest. Depolarization of embryonic cells by misexpression of KCNE1 non-cell-autonomously induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype. This effect is mediated by the up-regulation of Sox10 and Slug genes, thus linking alterations in ion channel function to the control of migration, shape, and mitosis rates during embryonic morphogenesis. Taken together, these data identify a role for the KCNQ1 channel in regulating key cell behaviors and reveal the molecular identity of a biophysical switch, by means of which neoplastic-like properties can be conferred upon a specific embryonic stem cell subpopulation.

PubMed ID: 18931301
PMC ID: PMC2575467
Article link: Proc Natl Acad Sci U S A
Grant support: 5K22DE16633 NIDCR NIH HHS, 5T32DE007327-07 NIDCR NIH HHS, R01-GM07742 NIGMS NIH HHS , K22 DE016633-04 NIDCR NIH HHS, K22 DE016633 NIDCR NIH HHS, T32 DE007327 NIDCR NIH HHS

Genes referenced: sox10 snai2 kcnq1 kcne1 dct atp6v0c gal.2 trpc2
Antibodies: Kcne1 Ab1 Kcnq1 Ab1 Kcnq1 Ab2


Article Images: [+] show captions
References:
Adams, 2006, Pubmed, Xenbase [+]


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