Nav: Home

Study provides better understanding of how brain tumors 'feed'

May 25, 2017

All cancer tumors have one thing in common - they must feed themselves to grow and spread, a difficult feat since they are usually in a tumor microenvironment with limited nutrients and oxygen. A study at The University of Texas MD Anderson Cancer Center has revealed new details about how an enzyme called acetyl-CoA synthetase 2 (ACSS2) allows brain tumors to grow despite their harsh surroundings. The findings, published in the May 25 online issue of Molecular Cell, portends ACSS2 as a potential player in new approaches to treating this often deadly disease.

ACSS2 provides tumors a competitive edge by enhancing their ability to use a cellular salt called acetate as a carbon-based food source rather than the more desirable glucose which is often in short supply in cancer cells. This lifeline allows cancer cells at the core of the tumor to survive and even grow as it battles with nutrient deficiency.

Current therapies and the body's own immune system are not efficient at stopping this vital nutrient pathway in cancer cells, and little is known about how these life-giving proteins are transported from cytosol, a liquid cell component, into the nucleus via a process called nuclear translocation. The ability to halt nuclear translocation of ACSS2 would cut off the cancer cell's self-maintaining ability at its most basic level. The study, led by Zhimin Lu, Ph.D., professor of Neuro-Oncology, provided new information about nuclear translocation and how ACSS2 may offer a new approach for therapy.

"Overcoming metabolic stress is a critical step in solid tumor growth. Acetyl coenzyme A (CoA) generated via glucose and acetate uptake is a key carbon source for important cellular processes such as histone acetylation and gene expression," said Lu. "However, how acetyl CoA is produced under nutritional stress is unclear. Our study explains the underlying mechanics of how this occurs, with ACSS2 as a novel and important method for gene expression under these circumstances."

Using a CRISPR gene editing process, Lu's team revealed what roles ACSS2 plays in histone acetylation by generation of nuclear acetyl-CoA from acetate within the cell's nucleus. It also demonstrated the significance of histone modification via a metabolic enzyme in maintaining cell stability and tumor development. Histones are proteins that act as spools around which DNA winds and are crucial to gene regulation, while histone acetylation is a modification process critical to gene expression.

In essence, ACSS2 gives genetic permission for the production of lysosomes, cellular structures that serve as the cell's waste disposal system, thus ridding the cell of unwanted materials, while recycling digested products for protein, DNA, and lipid synthesis. Lysosomes are recognized as a contributing factor in tumor development. ACSS2 also promotes a cannibalistic cell-feeding mechanism called autophagy, allowing lysosomes to receive, digest, and recycle much-needed nutrients. When nutrients located outside of the cell are limited, ACSS2 is able to reprogram cancer cell metabolism by increasing autophagy and reusing lysosome-digested products from unwanted or stored materials for cell survival and growth.

"These findings elucidate an instrumental interplay between reprogramming of metabolism and gene expression in cancer cells," said Lu. "Inhibition of both ACSS2's nuclear function and the metabolic pathway known as glycolysis, which converts glucose to tumor-feeding energy, appears to be an efficient approach for cancer treatment."
-end-
MD Anderson research team members included Xinjian Li, Ph.D., Xu Qian, Ph.D., Yan Xia, Ph.D., Yanhua Zheng, Ph.D., and Jong-Ho Lee, Ph.D., all of Neuro-Oncology; and Ganesh Rao, M.D., Neurosurgery. Other participating institutions included Duke-NUS Medial School, Singapore; Wenzhou Medical University, Wenzhou, China; Qingdao University Cancer Institute, Qingdao, China; and San Yat-Sen University Cancer Center, Guangzhou, China.

The study was funded by the National Institutes of Health (CA109035, CA169603, CA204996, NS089754, CA016672 and CA127001); the James S. McDonnell Foundation 21st Century Science Initiative in Brain Cancer Research Award (220020318); the National Natural Science Foundation of China (8167282 and 81472386); the MD Anderson Odyssey Fellowship; the Anne Eastland Spears Fellowship in GI Cancer Research; the Caroline Ross Endowed Fellowship; and the Harold C. and Mary L. Daily Endowment Fund Fellowship. Lu is a Ruby E. Rutherford Distinguished Professor.

University of Texas M. D. Anderson Cancer Center

Related Cancer Cells Articles:

Scientists have identified the presence of cancer-suppressing cells in pancreatic cancer
Researchers have identified cells containing a protein called Meflin that has a role in restraining the progression of pancreatic cancer.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
Brain cancer: Typical mutation in cancer cells stifles immune response
The exchange of a single amino acid building block in a metabolic enzyme can lead to cancer.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.
An index measures similarity between cancer cells and pluripotent stem cells
The new methodology measures tumor aggressiveness and the risk of relapse, helping doctors plan treatment, according to Brazilian scientists authors of a paper published in a special issue of the journal Cell.
More Cancer Cells News and Cancer Cells Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.