Irvine, CA – June 25, 2021 – New research from the University of California, Irvine, shows how circadian regulation of glucose production in the liver is lost during lung cancer progression, and how the resulting increase in glucose production can fuel cancer cell growth .
The new study, titled “Glucagon Regulates the Stability of REV-ERBα to Modulate Hepatic Glucose Production in a Model of Lung Cancer-Associated Cachexia,” published today in Scientific advances, illustrates how the circadian clock is regulated under stressful conditions, such as during the progression of lung cancer and a cancer-associated tissue atrophy disease called cachexia.
“Our research shows that a critical circadian protein, REV-ERB ?, controls glucose production in the liver. As lung cancer progresses, and especially in cachexia conditions, this circadian regulation is lost, resulting in increased glucose production from the liver, ”said senior author Selma Masri, PhD, assistant professor in the Department of Biological Chemistry at the UCI School of Medicine. “Based on our results, we found that lung tumors of the liver can provide instructive clues to increase glucose production, an important source of fuel for cancer cells.”
This research presents the circadian clock as a central regulator of glucose production during the progression of lung cancer and provides important insights for the development of novel therapeutics against REV-ERB? to suppress the growth of cancer cells.
“We continue to study the consequences of increased glucose production during lung cancer progression by tracking the metabolic fate of this newly generated glucose to determine whether this fuel source can fuel the increased metabolic needs of lung cancer cells,” said Amandine Verlande, PhD, and Sung Kook Chun, PhD, postdoctoral fellow at the Masri Laboratory.
The circadian clock is our intrinsic biological pacemaker that maintains physiological homeostasis in all tissues in the body. Under stressful conditions, the biological clock is rewired as an adaptive mechanism to maintain synchronicity and balance throughout the body.
This research was supported in part by the National Institutes of Health, the Concern Foundation, the V Foundation for Cancer Research, the Cancer Research Coordinating Committee, and shared resources supported by the UCI Chao Family Comprehensive Cancer Center.
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