UW-Madison: Cancer-signalling pathway could illuminate new avenue to therapy

Contact: Susan Smith, (608) 890-5643, ssmith5@uwhealth.org

Madison – Researchers from the University of Wisconsin School of Medicine and Public Health and Carbone Cancer Center have better defined a pro-growth signaling pathway common to many cancers that, when blocked, kills cancer cells but leaves healthy cells comparatively unharmed.  

The study, published Nov. 21  in the journal Nature Cell Biology, could establish new avenues of therapeutic treatments for many types of solid tumors.  

Growth signals typically come in the form of chemical agonists outside of cells that bind to protein receptors on cells. Activated receptors are responsible for transmitting the signal to the inside of the cell, ultimately generating a growth messenger called PIP3. Two years ago, research out of UW-Madison Professor Richard Anderson’s lab found that some of these agonist-stimulated receptors continue to transmit the signal even after they have been pulled into the cell, sequestered in vesicles called endosomes and presumably on their way to being degraded. 

“According to dogma in the literature, receptors shouldn’t make PIP3 at these internal sites, but they were,” Anderson says. “We set out to ask, ‘Why is that?'” 

In this new study, a postdoctoral fellow in Anderson’s lab, Suyong Choi, showed that the proteins known to be in this signal transmission cascade were all present on endosomes inside the cell, supporting the idea that the key growth message was being signaled from these internal compartments. However, there was one fact which they could not biologically explain: In a typical signaling cascade, each step amplifies the signal, suggesting there should be more and more of the messenger molecules; but here, levels of PIP3 and other intermediary messengers were too low to be detected in endosomes. 

“A scaffold completely solves this issue, because it acts like an assembly line, bringing together all of the proteins and passing one messenger molecule to the next protein in the cascade until the last protein, PI3K, is activated and generates PIP3,” Anderson says. “Suyong Choi found that the scaffolding protein IQGAP1 brings all of these proteins together like a happy family on the endosome. It’s an incredibly efficient mechanism.”  

READ MORE AT http://news.wisc.edu/cancer-signaling-pathway-could-illuminate-new-avenue-to-therapy/