Cholesterol Promotes Cancer

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 at the University of Illinois at Chicago, publish their findings in Nature Communications.

The new study explains how cholesterol promotes cancer by binding to a protein involved in signaling a pathway that encourages cell growth and division.

Previous studies have connected cholesterol to certain cancers. For example,  researchers 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 the research 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.

Their research points to a new regulatory role for cholesterol, and also presents an exciting new therapeutic target for suppressing canonical Wnt signaling to treat or prevent cancer.

Cholesterol prompts signal to be sent along canonical Wnt pathway

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:

"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, the research 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.

Additionally, the researchers found that cholesterol increases within the cell membrane appeared to favor canonical Wnt signaling over non-canonical Wnt signaling. The research team says this may explain why higher cholesterol levels increase cancer risk.

The team says their findings could yield a therapeutic target, and 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.

The research team knows that things like high-fat diets, which boost cholesterol levels, have been linked to an elevated incidence of cancer. Their 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.