Cholesterol activates signaling pathway that promotes cancer

July 15, 2014
This image depicts UIC chemistry professor Wonhwa Cho. Credit: UIC Photo Services

Everyone knows that cholesterol, at least the bad kind, can cause heart disease and hardening of the arteries. Now, researchers at the University of Illinois at Chicago describe a new role for cholesterol in the activation of a cellular signaling pathway that has been linked to cancer.

The finding is reported in Nature Communications.

Cells employ thousands of signaling pathways to conduct their functions. Canonical Wnt signaling is a pathway that promotes cell growth and division and is most active in embryonic cells during development. Overactivity of this signaling pathway in mature cells is thought to be a major driver in the development of cancer.

"Our research points to a new regulatory role for cholesterol, and also presents an exciting new for suppressing canonical Wnt signaling to treat or prevent cancer," said Wonhwa Cho, professor of chemistry at UIC and principal investigator of the research.

Cho and his colleagues were searching for novel cholesterol-binding proteins when they discovered a binding site for cholesterol on a protein called Dishevelled. Dishevelled is involved in canonical Wnt signaling and in non-canonical Wnt signaling, which plays a role in processes like cell movement and organization. Dishevelled is like a switch on the track—when the signal reaches Dishevelled, the signal is directed along either the canonical or non-canonical Wnt pathway. But until now, any factor governing activation of one pathway over the other was unknown, Cho said.

"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," he said.

The researchers found that when cholesterol is bound to Dishevelled, the signal continues along the canonical Wnt . Without cholesterol, canonical Wnt signaling cannot occur.

They also noticed that localized increases in cholesterol within cell membrane seemed to selectively promote canonical Wnt signaling over non-canonical Wnt signaling—a finding, Cho said, that might explain why elevated cholesterol increases cancer risk.

"We know that things like high-fat diets, which boost , have been linked to an elevated incidence of cancer," he said. "Our research provides a mechanism for how cholesterol promotes pathways that lead to cancer."

It also presents a possible therapeutic target. A drug that interferes with the binding of to Dishevelled, Cho said, may be effective against those cancers that are driven by canonical Wnt —a list that includes colon cancer, melanoma, breast cancer and lung .

Explore further: Researchers offer new insights on cancer cell signaling

Related Stories

Researchers offer new insights on cancer cell signaling

July 12, 2013
(Medical Xpress)—A pair of studies by a team of University of Notre Dame researchers led by Crislyn D'Souza-Schorey, professor of biological sciences, sheds light on a biological process that is activated across a vast ...

Cholesterol helps regulate key signaling proteins in the cell

December 19, 2012
Cholesterol plays a key role in regulating proteins involved in cell signaling and may be important to many other cell processes, an international team of researchers has found.

Link between colon cancer and metabolism identified

May 13, 2014
More than 60 years ago Otto Warburg recognized that cancer cells differ from normal cells in the metabolic pathway they use for the oxidation of sugar. Rather than the typical series of oxidative steps that take place in ...

Damage control: Recovering from radiation and chemotherapy

April 30, 2014
Researchers at the University of California, San Diego School of Medicine report that a protein called beta-catenin plays a critical, and previously unappreciated, role in promoting recovery of stricken hematopoietic stem ...

Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved

May 30, 2012
Breast-cancer researchers at the University of Wisconsin-Madison have found that two related receptors in a robust signaling pathway must work together as a team to maintain normal activity in mammary stem cells.

Stem cells found to play restorative role when affecting brain signaling process

June 5, 2014
A study by a Korean team of neuroscientists has concluded that when mesenchymal stem cells (MSCs; multipotent structural stem cells capable of differentiation into a variety of cell types) are transplanted into the brains ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

4 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Egleton
not rated yet Jul 15, 2014
Thanks guys.
I shall adjust my diet accordingly.
This ties in with Bruce Lipton's model.
https://www.youtu...0xVM4x1I
I would like to know if cancer cells have any Laertril receptors.
snowflake0446
5 / 5 (1) Jul 15, 2014
To the writer's first sentence: Apparently not everyone knows what causes hardening of the arteries: http://www.nhlbi....es.html. Read the first sentence. Stop pushing global gossip as truth. Also what about Enterobacter hormaechei from this article on your web site back in 2011: http://phys.org/n...is.html. Apparently Dr. Kozarov doesn't believe that anymore either...he's someone. Isn't he?
MisterM8
5 / 5 (1) Jul 16, 2014
Cholesterol has such a bad rap... Of course it's involved with cellular growth pathways; it's a very important molecule for cellular repair! In the future please make sure to delineate between cholesterol and cholesterol carriers, and the various types thereof. Knowledge without thoroughness is bread without butter.
snowflake0446
not rated yet Jul 20, 2014
MisterM8, I certainly agree with you. I fear the residual affects of Dr. Ancel Keys are still with us.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.