Nav: Home

Yale Cancer Center researchers find key to help treat different cancers

September 10, 2019

New Haven, Conn. -- Yale Cancer Center (YCC) scientists have uncovered the workings of a metabolic pathway or "gauge" that lets cancer cells detect when they have enough nutrients around them to grow. The researchers hope that drugs designed to turn down the gauge may eventually aid in treating many forms of cancer. Their findings were published in the journal Oncogene.

"The cancer cell has an unlimited appetite for nutrients," said Xiaoyong Yang, Ph.D., associate professor of comparative medicine and of cellular and molecular physiology at YCC and senior author of the study. "But in many parts of the body, especially for solid tumors, nutrients and oxygen are often limited, so the cell has to make a decision to grow or survive. We have shown how the cell adapts to its microenvironment, detecting nutrient availability to make this decision."

Yang and his colleagues studied the role of a process called O-GlcNAc protein modification in cancer metabolism. O-GlcNAc modification alters the function of proteins by attaching certain kinds of sugar molecules and is thought to generally act as a nutrient sensor for the cell. Yang noted "we were interested in this modification because it is a common feature across many types of cancer."

The YCC team began by examining a wide range of human cancer tissue samples for signs of O-GlcNAc modification, including levels of expression for the OGT and OGA enzymes. They found that both OGT and OGA are expressed at higher levels in many cancers than in normal tissues. Next, the investigators discovered that OGA also promotes tumor growth and metabolic reprogramming in cancer cells. They followed up to show OGA does so by altering acetylation of a protein known as PKM2 (a key player in cell metabolism), and this activity increases along with levels of glucose available to the cell. OGT then inhibits PKM2 activity via O-GlcNAc modification, which drives metabolic reprogramming and promotes tumor growth.

The result was a surprise, since scientists previously thought that OGA and OGT directly work against each other. "People always thought they were foes, and our study identified how they can be friends," Yang said. "These two opposing enzymes work together in a nutrient-rich environment to drive cancer cells to grow and reproduce."

Yang now hopes to develop drugs that can mislead the OGA/OGT metabolic gauge, "so that cancer cells don't decide to turn on aerobic glycolysis and grow even when nutrients are flowing freely," he said.

This OGA/OGT biological pathway is also working at much lower levels in normal cells, so the drugs would aim to reduce the pathway rather than block it completely. Yang's team is collaborating with biochemist colleagues to investigate compounds that target the enzymes. The researchers hope to eventually see if such compounds can be combined effectively with other drugs to treat many forms of cancer.
-end-
Jay Prakash Singh is lead author on the paper. Other Yale contributors include Kevin Qian, Jeong-Sang Lee, Bichen Zhang, Qunxiang Ong, Weiming Ni, Hai-Bin Ruan, Min-Dian Li, Kaisi Zhang, Jing Wu, Raimund Herzog, Susan Kaech and Robert Sherwin.

This work was supported by grants from the NIH (R01 DK089098, P01 DK057751), Yale Cancer Center, and the American Cancer Society.

Yale 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.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...