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How to reset a diseased cell

Date:
May 1, 2015
Source:
University of California, San Diego Health Sciences
Summary:
In proof-of-concept experiments, researchers demonstrate the ability to tune medically relevant cell behaviors by manipulating a key hub in cell communication networks. The manipulation of this communication node makes it possible to reprogram large parts of a cell's signaling network instead of targeting only a single receptor or cell signaling pathway.
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In proof-of-concept experiments, researchers at University of California, San Diego School of Medicine demonstrate the ability to tune medically relevant cell behaviors by manipulating a key hub in cell communication networks. The manipulation of this communication node, reported in this week's issue of Proceedings of the National Academy of Sciences, makes it possible to reprogram large parts of a cell's signaling network instead of targeting only a single receptor or cell signaling pathway.

The potential clinical value of the basic science discovery is the ability to eventually develop techniques -- drugs or gene therapy approaches, for example -- that could slow or reverse the progression of diseases, such as cancer, which are driven by abnormal cell signaling along multiple upstream pathways.

"Our study shows the feasibility of targeting a hub in the cell signaling network to reset aberrant cell signaling from multiple pathways and receptors," said senior author Pradipta Ghosh, MD, an associate professor of medicine.

Specifically, the UC San Diego team has engineered two peptides -- protein fragments -- to either turn on or turn off activity in a family of proteins called G proteins.

G protein-coupled receptors, commonly found on the surface of cells, enable cells to sense and respond to what is happening around them. About 30 percent of all prescription drugs affect cells via G protein-coupled receptors.

Researchers, including members of the UC San Diego team, recently discovered that G proteins can also be activated inside cells -- not just on cell membranes -- by other receptors, including a protein called GIV. Its activity is implicated in cancer metastasis and other disease states. Both the "on" and "off" peptides were made from a piece of the GIV protein receptor.

In a series of cell culture experiments, the "on" peptides were shown to accelerate cells' ability to migrate after scratch-wounding, a process linked to wound healing. The "off" peptide, in contrast, reduced the aggressiveness of cancer cells and reduced the production of collagen by cells associated with liver fibrosis. In experiments with mice, the topical application of the "on" peptides helped skin wounds heal faster.

"The takeaway is that we can begin to tap an emerging new paradigm of G protein signaling," Ghosh said.


Story Source:

Materials provided by University of California, San Diego Health Sciences. Original written by Christina Johnson and Scott LaFee. Note: Content may be edited for style and length.


Journal Reference:

  1. Gary S. Ma, Nicolas Aznar, Nicholas Kalogriopoulos, Krishna K. Midde, Inmaculada Lopez-Sanchez, Emi Sato, Ying Dunkel, Richard L. Gallo, Pradipta Ghosh. Therapeutic effects of cell-permeant peptides that activate G proteins downstream of growth factors. Proceedings of the National Academy of Sciences, 2015; 201505543 DOI: 10.1073/pnas.1505543112

Cite This Page:

University of California, San Diego Health Sciences. "How to reset a diseased cell." ScienceDaily. ScienceDaily, 1 May 2015. <www.sciencedaily.com/releases/2015/05/150501125445.htm>.
University of California, San Diego Health Sciences. (2015, May 1). How to reset a diseased cell. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2015/05/150501125445.htm
University of California, San Diego Health Sciences. "How to reset a diseased cell." ScienceDaily. www.sciencedaily.com/releases/2015/05/150501125445.htm (accessed March 28, 2024).

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