Researchers, including those of Indian-origin, have found a new electrical mechanism that can control molecular switches which regulate human cell growth and are linked to life-threatening cancers.
The finding can help develop treatments for some of the most lethal types of cancer including pancreatic, colon and lung, which are characterised by uncontrolled cell growth caused by breakdowns in cell signalling cascades, researchers said.
The molecular switches regulating human cell growth do a great job of replacing cells that die during the course of a lifetime. But when they misfire, life-threatening cancers can occur.
The research focused on a molecular switch called K-Ras.
Mutated versions of K-Ras are found in about 20 per cent of all human cancers in the US and these mutations lock the K-Ras switch in the on position.
“When K-Ras is locked in the on position, it drives cell division, which leads to the production of a cancer,” said senior author John Hancock, from University of Texas Health Science Centre at Houston (UTHealth) Medical School in US.
“We have identified a completely new molecular mechanism that further enhances the activity of K-Ras,” Hancock said.
The study focused on the tiny electrical charges that all cells carry across their limiting (plasma) membrane.
“What we have shown is that the electrical potential (charge) that a cell carries is inversely proportional to the strength of a K-Ras signal,” Hancock said.
With the aid of a high-powered electron microscope, the investigators observed that certain lipid molecules in the plasma membrane respond to an electrical charge, which in turn amplifies the output of the Ras signalling circuit. This is like a transistor in an electronic circuit board.
“Our results may finally account for a long-standing but unexplained observation that many cancer cells actively try to reduce their electrical charge,” said first author Yong Zhou, assistant professor of integrative biology and pharmacology at UTHealth Medical School.
Initial work was done with human and animal cells and findings were subsequently confirmed in a fruit fly model on membrane organisation.
“Beyond the immediate relevance to K-Ras in cancer, it is a completely new way that cells can use electrical charge to control a multitude of signalling pathways, which may be particularly relevant to the nervous system,” Hancock said.
Hancock’s co-authors include Dhananjay Thakur and Kartik Venkatachalam of The University of Texas Graduate School of Biomedical Sciences. The study was published in the journal Science.
