Nav: Home

Metabolite that promotes cancer cell transformation and colorectal cancer spread identified

December 01, 2016

A metabolite is found to make the colorectal cancer cells more invasive and increase likelihood of more tumors spreading to distant organs; this makes the metabolite a promising target for future cancer therapies

Osaka, Japan - Cancer cells exhibit a range of properties that diverge from those of their normal healthy counterparts, including levels of various metabolites. However, it has been difficult to determine whether such altered levels is a cause or a consequence of the cancerous growth.

In a breakthrough that offers hope for improved treatment of colorectal cancer, Osaka University researchers have identified a metabolite that causes cancer cells to develop more dangerous properties and increases the likelihood that cancer will spread in colorectal cancer patients.

The team examined different varieties of cancer cells and cells from normal tissues and revealed high levels of D-2-hydroxyglutarate (D-2HG) in colorectal cancer cells. They then administered either D-2HG into cancer cells and found it induced the cells to undergo transformation. This transformation involved the cells adhering less strongly to each other and migrating more easily. These properties in the body are associated with cancer progression and spread.

"When we grew the cells with D-2HG on plates and measured their movement, they migrated further than untreated cells" lead author Hugh Colvin says. "Using a Matrigel assay that models the ability of cancer cells to enter local tissue, the D-2HG treated cells were also more invasive."

The researchers showed that D-2HG acts by increasing the expression of a gene called ZEB1, which promotes this cell transformation. They also obtained specimens from 28 human colorectal cancer patients and divided them into two groups with low or high levels of D-2HG. The patients' records showed that the high group had more often suffered cancer spread to distant organs, which suggested the importance of D-2HG in patient prognosis.

"When cancer cells initially emerge, it can be difficult for them to survive and multiply because of the local conditions," coauthor Hideshi Ishii says. "D-2HG makes cancer cell survival more likely by causing them to transform from epithelial to mesenchymal cells, meaning that they can invade local tissue, enter the blood, and be transported elsewhere to establish a new tumor."

With the importance of this molecule in cancer progression and prognosis revealed, it can be focused on as a promising target for colorectal cancer treatments.

-end-



Osaka University

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: Radiolab

Radiolab Presents: Anna in Somalia
This week, we are presenting a story from NPR foreign correspondent Gregory Warner and his new globe-trotting podcast Rough Translation. Mohammed was having the best six months of his life - working a job he loved, making mixtapes for his sweetheart - when the communist Somali regime perp-walked him out of his own home, and sentenced him to a lifetime of solitary confinement.  With only concrete walls and cockroaches to keep him company, Mohammed felt miserable, alone, despondent.  But then one day, eight months into his sentence, he heard a whisper, a whisper that would open up a portal to - of all places and times - 19th century Russia, and that would teach him how to live and love again. 
Now Playing: TED Radio Hour

Future Consequences
From data collection to gene editing to AI, what we once considered science fiction is now becoming reality. This hour, TED speakers explore the future consequences of our present actions. Guests include designer Anab Jain, futurist Juan Enriquez, biologist Paul Knoepfler, and neuroscientist and philosopher Sam Harris.