Transmembrane voltage potential of somatic cells controls oncogene-mediated tumorigenesis at long-range

摘要: The microenvironment is increasingly recognized as a crucial aspect of cancer. In contrast and complement to the field's focus on biochemical factors extracellular matrix, we characterize novel host:tumor interaction - endogenous bioelectric signals among non-excitable somatic cells. Extending prior work focused state cancer cells themselves, show for first time that resting potentials distant are critical oncogene-dependent tumorigenesis. Xenopus laevis tadpole model, used human oncogenes such mutant KRAS drive formation tumor-like structures exhibited overproliferation, increased nuclear size, hypoxia, acidity, leukocyte attraction. Remarkably, misexpression hyperpolarizing ion channels at sites within significantly reduced incidence these tumors. suppression tumorigenesis could also be achieved by hyperpolarization using native CLIC1 chloride channels, suggesting treatment modality not requiring gene therapy. Using dominant negative approach, implicate HDAC1 mechanism which potential changes affect downstream cell behaviors. Based published data voltage-mediated butyrate flux through SLC5A8 transporter, present model linking host ability initiate Antibiotic suggest relevant generated bacterial species, identifying link between microbiome mediated alterations in signaling.