Researchers find new trigger for onset of colon cancer, which may lead to better therapies

April 2, 2018, Dartmouth-Hitchcock Medical Center

Colon cancer is the second most common cause of cancer-related deaths. The APC protein has long been known for its critical role in preventing colorectal cancer. When APC is inactivated, the development of colorectal cancer is triggered. Inactivation of APC is responsible for the vast majority (80%) of all colorectal cancers. Researchers from the laboratory of Yashi Ahmed, MD, PhD at Dartmouth's Norris Cotton Cancer Center, in collaboration with the groups of Ethan Lee, MD, PhD at Vanderbilt University and David Robbins, PhD at the University of Miami's Sylvester Comprehensive Cancer Center, have identified a new function for this colon cancer gene: APC stops several colon cancer activators.

APC works in a that allows one cell to communicate with its neighbors. When APC is inactivated, this pathway goes into overdrive and that triggers development. Exactly how APC acts in this pathway has remained a mystery. The long-held view was that the sole function of APC is to cause the destruction of one activator of the overdrive activity. "The surprise from our research is that APC actually has a second role in putting the brakes on several other activators in the pathway," says Ahmed. "This work changes our view of how this key gene acts, revealing that APC's role is much broader and multi-faceted."

The team's work, "APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway" has been published as a feature article in Developmental Cell.

This new finding about the way that APC blocks the development of colorectal may lead to new therapeutic targets to combat this disease. "Because this new role of APC involves proteins on the cell surface, targeting colorectal cancers may become easier," says Ahmed. "For example, therapeutic antibodies, which normally cannot work inside the cell, can now be used to treat that have APC mutations."

Figuring out the exact way in which APC stops colon cancer activator proteins will hopefully allow researchers in the future to identify additional drug targets, and to better design therapies for colon cancer patients that kill cancer cells but spare the normal in the colon. "The discovery of the new role of APC may also help us understand why APC mutations are so prevalent in certain cancers but not others," says Lee. "Certain tissues may have a backup mechanism to put the brakes on the pathway when APC is mutated."

Explore further: Researchers publish new findings on influence of high-fat diet on colorectal cancer

More information: Kenyi Saito-Diaz et al, APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway, Developmental Cell (2018). DOI: 10.1016/j.devcel.2018.02.013

Related Stories

Researchers publish new findings on influence of high-fat diet on colorectal cancer

July 6, 2017
Poor diet is associated with 80% of colorectal cancer cases, but the exact pathways by which diet leads to cancer are not known.

Hedgehog signaling proteins keep cancer stem cells alive

January 22, 2018
Researchers from Charité - Universitätsmedizin Berlin have discovered that the survival of cancer stem cells is dependent on the Hedgehog signaling pathway. Targeting this pathway had previously shown no effect on the growth ...

New study offers novel treatment strategy for patients with colon cancer

September 20, 2017
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide.

Researchers recommend specific diets for preventing colorectal cancer in high-risk groups

December 22, 2017
Colorectal cancer is the most prevalent malignant tumour in Spain. It is known that factors such as diet and intestinal inflammation play an important role in its occurrence, but direct links between nutrients, inflammation ...

'Fusion genes' drive formation and growth of colorectal cancer

July 12, 2017
Genetic mutations caused by rearranged chromosomes drive the development and growth of certain colorectal cancers, according to new research conducted by Weill Cornell Medicine investigators.

Recommended for you

Single-cell study in a childhood brain tumor affirms the importance of context

April 20, 2018
In defining the cellular context of diffuse midline gliomas, researchers find the cells fueling their growth and suggest a potential approach to treating them: forcing their cells to be more mature.

Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

April 20, 2018
Difficult to treat and aggressive "triple-negative" breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center ...

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

0 comments

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.