Using optogenetics to control electric signaling in cells may prevent, normalize tumors

Researchers at Tufts University (Medford/Somerville, MA) demonstrated the possibility of preventing tumors from forming and normalizing tumors after they have formed by using optogenetics to control electrical signaling among cells. The technique, done in a frog model, allowed the research team to specifically manipulate bioelectrical signals to both prevent and cause regression of tumors induced by oncogenes.

Related: Optogenetics tools address a growing range of applications

Virtually all healthy cells maintain a more negative voltage in the cell interior compared with the cell exterior—the opening and closing of ion channels in the cell membrane can cause the voltage to become more positive (depolarizing the cell) or more negative (polarizing the cell). Tumors can be detected by their abnormal bioelectrical signature before they are otherwise apparent.

Lead author Brook Chernet, Ph.D., injected cells in Xenopus laevis embryos with RNA encoding a mutant RAS oncogene known to cause cancer-like growths. The researchers also expressed and activated either a blue light-activated, positively charged ion channel, ChR2D156A, or a green light-activated proton pump, Archaerhodopsin (Arch), both of which hyperpolarize frog embryonic cells, thereby inducing an electric current that caused the cells to go from a cancer-like depolarized state to a normal, more negative polarized state. Activation of both agents significantly lowered the incidence of tumor formation and also increased the frequency with which tumors regressed into normal tissue.

"This provides proof of principle for a novel class of therapies which use light to override the action of oncogenic mutations," says senior and corresponding author Michael Levin, Ph.D., who holds the Vannevar Bush chair in biology and directs the Center for Regenerative and Developmental Biology at Tufts School of Arts and Sciences. "Using light to specifically target tumors would avoid subjecting the whole body to toxic chemotherapy or similar reagents."

Full details of the work appear in the journal Oncotarget; for more information, please visit http://dx.doi.org/10.18632/oncotarget.8036.

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