The deleterious effects of high cholesterol – particularly LDL, the “bad” kind – are well known and include heart disease, stroke and atherosclerosis. But in a new study, researchers have discovered how cholesterol activates a cellular signaling pathway linked to cancer.
The researchers, led by Prof. Wonhwa Cho, professor of chemistry from the University of Illinois at Chicago, publish their findings in Nature Communications.
Previous studies have connected cholesterol to certain cancers. For example, Medical News Today recently reported on a study that linked high cholesterol to increased breast cancer risk.
But for this latest study, the researchers focused on signaling pathways, which cells employ to carry out their activities. They explain that a pathway called canonical Wnt signaling encourages cell growth and division, an important function for development in embryonic cells.
However, in mature cells, overactivity of this pathway is believed to be a major promoter of cancer development.
When Prof. Cho and his team were searching for new cholesterol-binding proteins, they found a binding site for cholesterol located on a protein known as “Dishevelled.” This protein is involved in both canonical Wnt signaling and non-canonical Wnt signaling, which the team says is involved in cell movement and organization.
“Our research points to a new regulatory role for cholesterol,” says Prof. Cho, “and also presents an exciting new therapeutic target for suppressing canonical Wnt signaling to treat or prevent cancer.”
The team further describes Dishevelled as “a switch on the track,” meaning that when a signal reaches the protein, it directs the signal along either the canonical or the non-canonical Wnt pathway.
However, until now, it was unknown as to whether any particular element governed the decision for the protein to direct the signal down one pathway over the other.
This is where cholesterol comes in, explains Prof. Cho:
“Once we realized that cholesterol is able to bind specifically to Dishevelled, we became interested in cholesterol as a potential determinant of which of the Wnt signaling pathways gets activated.”
In detail, he and his team discovered that when cholesterol binds to Dishevelled, it sends the signal along the canonical Wnt signaling pathway – which encourages cell growth and division. Without cholesterol, this type of signaling cannot happen, they add.
Additionally, the researchers found that cholesterol increases within the cell membrane appeared to favor canonical Wnt signaling over non-canonical Wnt signaling. Prof. Cho says this may explain why higher cholesterol levels increase cancer risk.
The team says their findings could yield a therapeutic target, and Prof. Cho says a drug that prevents cholesterol from binding to Dishevelled could be effective against canonical Wnt signaling-driven cancers. This could include colon cancer, melanoma, breast cancer and lung cancer.
“We know that things like high-fat diets, which boost cholesterol levels, have been linked to an elevated incidence of cancer,” he says. “Our research provides a mechanism for how cholesterol promotes pathways that lead to cancer.”
A study recently published in the journal Cell Reports suggested that “bad” cholesterol is an important culprit in metastasis, the spread of cancer.