Potential therapeutic target for wound-healing and cancer identified

A Jackson Laboratory research team led by Professor Lenny Shultz, Ph.D., reports that a protein involved in wound healing and tumor growth could be a potential therapeutic target.

In one of nature's mixed blessings, the mechanisms that work to heal cuts and wounds, rebuilding damaged cells, can also go out of control and cause cancer. But understanding those mechanisms could lead to new ways of stimulating healing in wound patients and dialing back cancerous proliferation.

An inactive rhomboid protease, iRhom2, is normally a short-lived protein that controls a cascade of events involved in as well as . By introducing mutations in Rhbdf2, the gene that encodes the iRhom2 protein, the researchers extended the protein's duration and wound-healing power. And while the altered protein also contributed to the growth of already-present tumors, it did not trigger the spontaneous development of new tumors.

Epidermal growth factor receptor (EGFR) signal transduction plays a major role in growth, proliferation and differentiation of mammalian cells. "In Drosophila," explains Vishnu Hosur, a postdoctoral associate in the Shultz lab, "iRhoms, are cardinal regulators of EGFR signaling. In humans, iRhoms have been implicated in EGFR-mediated keratinocyte proliferation and cancer growth, but the molecular mechanisms underlying these have not been well defined."

In this study, the researchers used molecular, cell biological, in vivo genetic and bioinformatics approaches to identify the EGFR ligand amphiregulin as a physiological substrate, and demonstrate a role for iRhoms in amphiregulin-EGFR-dependent wound healing. Furthermore, they showed how iRhom mutations that increase EGFR signaling, under the right circumstances, can drive cancer development.

"This study demonstrates the significance of mammalian iRhoms in regulating an EGFR signaling event that promotes accelerated wound healing and triggers tumorigenesis," Shultz says. "It provides a paradigm shift in our understanding of rhomboid enzymes and their emerging role in diverse biological functions. Given their ability to regulate EGFR signaling in parallel with metalloproteases, iRhoms can be in impaired wound healing and cancer."

add to favorites email to friend print save as pdf

Related Stories

The right combination: Overcoming drug resistance in cancer

Jun 01, 2012

Overactive epidermal growth factor receptor (EGFR) signaling has been linked to the development of cancer. Several drug therapies have been developed to treat these EGFR-associated cancers; however, many patients have developed ...

Recommended for you

Putting the brakes on cancer

Dec 19, 2014

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

Peanut component linked to cancer spread

Dec 19, 2014

Scientists at the University of Liverpool have found that a component of peanuts could encourage the spread and survival of cancer cells in the body.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.