Boffins identify ‘cross-talk’ mechanism that contributes to colorectal cancer

WASHINGTON - Scientists from University of Wisconsin-Madison School have identified what they call ‘cross-talk’ mechanism that appears to contribute to colorectal cancer.

This molecular mechanism allows two powerful signalling pathways to interact and begin a process leading to colorectal tumours.

“We are very excited about these findings,” said Vladimir Spiegelman, an associate professor of dermatology.

“Drugs could be developed to block this mechanism and prevent colorectal cancer, which affects millions of people worldwide,” Spiegelman added.

They focused their research on the Wnt signaling pathway, which has been implicated in the vast majority of all colorectal cancers.

Like all signaling pathways, this one involves a group of molecules that work in sequence to perform a specific cell function. At each step along the way, the molecules perform tasks outlined in the signals until the job is finally done. If there’s a breakdown anywhere in the normal process, cancer can occur.

Previous study led by Spiegelman showed how signals in the Wnt pathway regulate CRD-BP, a gene that contributes to normal colorectal cells’ changing into tumour cells.

“Within the Wnt pathway, we found that CRD-BP binds to and increases the messenger RNA of a cancer-promoting transcription factor called GLI1,” Spiegelman said.

The scientists knew that GLI1 was also active in another signalling pathway, called Hedgehog, which is known to be associated with the development of several kinds of cancers although its role in colorectal cancer has been controversial. So they explored how the two pathways interact around CRD-BP and GLI1 messenger RNA.

“Scientists have postulated that these two pathways engage in cross-talk in different ways, but the mechanisms of how and where that happens have been unclear,” Spiegelman said.

Each pathway, he adds, contributes in important ways to normal embryonic development and stem-cell maintenance.

The team found that CRD-PB serves as the link between the Wnt and Hedgehog pathways.

Increased GLI1 then activates cancer-promoting genes that are usually considered downstream targets of the Hedgehog pathway.

The findings point to promising therapeutic possibilities, Spiegelman added.

The study appears in journal Cancer Research. (ANI)