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

Endogenous hormones improve breast cancer risk models

22 hours ago

(HealthDay)—Inclusion of endogenous hormones in prediction models improves prediction of invasive breast cancer risk in postmenopausal women, according to a study published online Aug. 18 in the Journal of ...

Novel oncogenic RET mutation found in small cell lung cancer

23 hours ago

For the first time an oncogenic somatic mutation at amino acid 918 in the RET (rearranged during transfection) protein has been identified in small cell lung cancer (SCLC) tumors and enforced expression of this mutation within ...

User comments