Cancer Center Discovery Has Therapeutic Targeting Potential

Researchers at the University of Illinois Cancer Center discovered a new player in a GPCR pathway, offering more insight into how blood vessels develop and feed tumor development.

The discovery is the first time that the sphingosine 1-phosphate (S1P) pathway, a known GPCR, has been linked to chloride intracellular channels 1 (CLIC1) and 4 (CLIC4), known broadly as CLIC proteins.

The S1P pathway promotes tumorigenesis and is considered critical to blood vessel development. CLIC proteins promote blood vessel development. However, despite the proposed channel mechanisms associated with CLICs, their mechanism of action remains unclear. Uncovering CLIC protein action as part of the S1P pathway helps scientists connect the dots about the function of the CLIC family and suggests new avenues for oncogenesis study.

“Understanding how CLIC proteins work remains a scientific challenge, and there is no consensus among scientists on their function. Previous studies have shown CLIC involvement in vascular development, but how it regulates vascular growth, or angiogenesis, remains unknown. Our findings show, for the first time, a connection between CLICs and GPCR signaling in vascular development, providing more insights to the function of the CLIC family,” said De Yu (Brian) Mao, PhD.

University of Illinois Cancer Center Director Jan Kitajewski’s laboratory team published their findings in the April 21 edition of Science Signaling.

“The implications of this work are many, starting with the fact that GPCR-CLIC signaling controls blood vessel function and continuing with the knowledge that GPCR are commonly the targets of new therapeutics,” Kitajewski said. “This knowledge improves our ability to target this pathway.”

The abstract and text of the article are available here.