Nav: Home

Body clock researchers prevent liver cancer growth in mice

November 07, 2018

The body's internal clock could play a critical role in the fight against certain types of liver cancer, according to a preclinical study by scientists from The University of Texas Health Science Center at Houston (UTHealth). The results were published recently in the journal Nature Communications.

The body's clock, called the circadian clock, is an intrinsic, 24-hour timekeeping system that operates in all cells of the body and regulates sleep, metabolism and other vital body functions.

"We were able to inhibit the growth of liver cancer in a mouse model by manipulating the circadian clock at the cellular level," said Kristin Eckel-Mahan, Ph.D., the study's senior author and an assistant professor with the Center for Metabolic and Degenerative Diseases at McGovern Medical School at UTHealth.

Eckel-Mahan said researchers confirmed their findings in human tissue samples.

In 2015, 32,908 new cases of liver cancer were reported, and 25,760 people died of liver cancer in the United States, reported the Centers for Disease Control and Prevention.

Eckel-Mahan's team identified a malfunctioning protein that was inhibiting the expression of a key circadian transcription factor and blocking the ability of a tumor suppressor to perform its normal 24-hour cellular functions. When investigators forced the tumor cells to re-express the deficient circadian protein, the tumor cells died.

Fifty percent of liver tumors express this malfunctioning protein, which induces circadian dysfunction in those cells, said Eckel-Mahan, whose laboratory is in the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth.

The study focused on hepatocellular carcinoma (HCC), the leading liver malignancy found in humans and the second-leading cause of all malignancy-related cancer deaths. Hepatocellular carcinoma is on the rise and has been linked to obesity-associated fatty liver disease.

"These results suggest that targeting the circadian clock in HCC may be a promising treatment for the growth and progression of HCC tumors," the authors wrote.

She said the next steps are to determine how to prevent disruption of the clock in the first place and to study whether pharmacological approaches known to improve clock function can also prevent the growth of these liver tumors.
-end-
Eckel-Mahan's UTHealth coauthors include Baharan Fekry, Ph.D. (lead author); Aleix Ribas Latre, Ph.D.; Corrine Baumgartner; Christopher Kwok; Rebecca Berdeaux, Ph.D.; Kai Sun, Ph.D.; Mikhail Kolonin, Ph.D.; Sidney Wang, Ph.D.; and Seung-Hee "Sally" Yoo, Ph.D. Also contributing to the research were Pooja Patel, Ph.D., and Loning Fu, Ph.D., of Baylor College of Medicine; and Frances Sladek, Ph.D., and Jonathan Deans, Ph.D., of the University of California, Riverside.

Sun, Kolonin, Wang, Yoo and Eckel-Mahan are on the faculty at The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. Kolonin is the holder of the Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research at McGovern Medical School.

The study, titled "Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma," was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NDK114037) and the American Cancer Society (RSG-17-215-01-C).

University of Texas Health Science Center at Houston

Related Tumor Cells Articles:

When healthy cells stimulate the migration of tumor cells
Estrogens act as a driving force of both healthy and cancerous mammary cell growth by binding to receptors that include GPER, which is generally located in cell membranes.
Tumor cells get stiff before becoming invasive
A study published now on Nature Communications shows that breast cancer cells undergo a stiffening state prior to acquiring malignant features and becoming invasive.
Tumor-trained T cells go on patrol
In cancer, immune cells infiltrate tumors -- but it hasn't been known which immune cells exit the tumor or where they go next.
Tumor-dwelling immune cells thwart cancer immunotherapy
Researchers have caught tumor-associated immune cells called macrophages in the act of stealing checkpoint inhibitor antibodies away from their intended T cell targets, and blocking this thievery led to improved therapeutic responses in tumor-bearing mice.
Are tumor cells glutamine addicts?
Many tumors are thought to depend on glutamine, suggesting glutamine deprivation as therapeutic approach, but a new study shows that this effect might have been overestimated.
More Tumor Cells News and Tumor Cells 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

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
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...