Researchers ‘Hack’ the Broken Cellular Signals Behind Cancer

Resetting the body's cancer trigger.

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May 2 2015, 12:00pm

Protein structures. Image: Wiki

"Hacking" is a fraught term when it comes to biology, so often taken up by body modification goofballs and-or those that envision biotechnology in its most science-fictional terms. But when it comes to a set of recent experiments conducted at the University of California, San Diego, it's hard to resist—researchers there have successfully manipulated the signalling capabilities of diseased human cells, allowing for a resetting of the cell's communications capabilities. The UCSD work is described in the current Proceedings of the National Academy of Sciences.

"Most common diseases (e.g., cancer, inflammatory disorders, diabetes) are driven by not one, but multiple cell surface receptors that trigger and sustain a pathologic signaling network," the researchers note. "The largest fraction of therapeutic agents that target individual receptors/pathways often eventually fail due to the emergence of compensatory mechanisms."

Commonly found on the surfaces of cells are what's known as G protein-coupled receptors (GPCRs), which are a crucial way cells use to sense and respond to the environment around them. These receptors work by chemically binding to molecules on the outside of the cell—representing odors, pheromones, light-sensitive compounds, hormones, and neurotransmitters—and passing a signal back into the guts of the cell, via a process that's still poorly understood. The result is a "conformal" change in the receptor protein, which is essentially an adjustment in how the protein is spatially situated or folded.

So, with the GPCRs activated, some signal is sent within the cell, triggering a cascade of messages usually resulting in the cell doing something, as mediated by G proteins, which are like on/off switches within a cell. A great many human diseases are involved in this signalling process and it's estimated that 40 percent of all pharmaceutical drugs act on GPCRs.

It was discovered fairly recently that it's possible to activate G proteins without the involvement of cell membrane-based (or outside) receptors. One mechanism is via the protein GIV, which is found on the inside of cells (as opposed to their outside environment) and can trigger signals potentially leading to the development of metastatic cancer and other disease states, but also some good things, like accelerated wound healing. One of the UCSD experiments involved the topical application of GIV proteins onto the wounds of lab mice (don't ask), with the result being a sharp improvement in healing time (the signalling proteins could be absorbed by cells).

The hacking accomplished by the UCSD team involved manipulating GIV proteins into on and off states, with the "on" configuration leading to functions involved in wound-healing and the "off" configuration leading to, among other things, less aggressive forms of cancer. GIV-associated peptides, or short molecular snippets of complete proteins, were found to enhance myriad processes, including "2D cell migration after scratch-wounding, invasion of cancer cells, and finally, myofibroblast activation and collagen production."

And these are likely to be just the first examples of a long list of cellular functions subject to manipulation via GIV peptides. At the very least, it offers the potential of resetting broken cellular signals, and much of the time that's all a disease is: a network glitch.