Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells
Open Access
- 28 October 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (43), 16608-16613
- https://doi.org/10.1073/pnas.0808328105
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 β-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.Keywords
This publication has 69 references indexed in Scilit:
- Nervous system KV7 disorders: breakdown of a subthreshold brakeThe Journal of Physiology, 2008
- Kv7.1 (KCNQ1) properties and channelopathiesThe Journal of Physiology, 2008
- KCNQ1 and KCNE1 K+ Channel Components are Involved in Early Left-Right Patterning in Xenopus laevis EmbryosCellular Physiology and Biochemistry, 2008
- H,K-ATPase protein localization and Kir4.1 function reveal concordance of three axes during early determination of left–right asymmetryMechanisms of Development, 2007
- Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B–Induced GliomagenesisMolecular Cancer Research, 2007
- Knockdown of Nav 1.6a Na+ channels affects zebrafish motoneuron developmentDevelopment, 2006
- Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast CancerPLoS Genetics, 2006
- Expression of the Transcription Factors Snail, Slug, and Twist and Their Clinical Significance in Human Breast CancerAnnals of Surgical Oncology, 2005
- Induction of Mitosis in Mature Neurons in Central Nervous System by Sustained DepolarizationScience, 1976
- Electrical stimulation of RNA and protein synthesis in the frog erythrocyteExperimental Cell Research, 1973