Glucagon regulates the stability of REV-ERBα to modulate hepatic glucose production in a model of lung cancer–associated cachexia

Verlande, Amandine; Chun, Sung Kook; Goodson, Maggie O; Fortin, Bridget M.; Bae, Hosung; Jang, Cholsoon; Masri, Selma

doi:10.1126/sciadv.abf3885

Cited by 21 publications

(19 citation statements)

References 78 publications

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“…An alternate approach may be to assess the state of the circadian clock before and after MYC inhibition not in the tumor, but in a more easily accessed part of the body such as the blood. There is evidence from mouse models that primary tumors may distally disrupt circadian clocks throughout the body [ 173 , 174 ]. In human studies, patients with disrupted circadian activity, melatonin, or cortisol rhythms (all of which are distal processes to most tumors) had poorer prognosis across a wide variety of cancers [ 47 , 48 , 49 , 50 , 51 , 52 ].…”

Section: Clinical Applications: Myc Inhibition and Measurement Of The Molecular Clock In Patientsmentioning

confidence: 99%

MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer

Burchett

Clark

Altman

2021

IJMS

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The MYC oncoprotein and its family members N-MYC and L-MYC are known to drive a wide variety of human cancers. Emerging evidence suggests that MYC has a bi-directional relationship with the molecular clock in cancer. The molecular clock is responsible for circadian (~24 h) rhythms in most eukaryotic cells and organisms, as a mechanism to adapt to light/dark cycles. Disruption of human circadian rhythms, such as through shift work, may serve as a risk factor for cancer, but connections with oncogenic drivers such as MYC were previously not well understood. In this review, we examine recent evidence that MYC in cancer cells can disrupt the molecular clock; and conversely, that molecular clock disruption in cancer can deregulate and elevate MYC. Since MYC and the molecular clock control many of the same processes, we then consider competition between MYC and the molecular clock in several select aspects of tumor biology, including chromatin state, global transcriptional profile, metabolic rewiring, and immune infiltrate in the tumor. Finally, we discuss how the molecular clock can be monitored or diagnosed in human tumors, and how MYC inhibition could potentially restore molecular clock function. Further study of the relationship between the molecular clock and MYC in cancer may reveal previously unsuspected vulnerabilities which could lead to new treatment strategies.

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Section: Clinical Applications: Myc Inhibition and Measurement Of The Molecular Clock In Patientsmentioning

confidence: 99%

MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer

Burchett

Clark

Altman

2021

IJMS

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“…Furthermore, unlikely other disease-related malnutrition, cancer-related malnutrition, are thought to be different from those that lack nutrients in the absence of underlying diseases (i.e., hunger and anorexia nervosa). It has been observed that metabolic changes in cancer patients, such as inflammation, increased catabolic rate, and ineffective cyclic anabolic resistance, achieved through a tumor or cancer treatment may invite malnutrition in the patient ( 111 , 112 ). Apart from other clinical aspects in cancer-related malnutrition, the lack of adequate knowledge of nutritional intervention for cancer patients in caregivers is also a significant contribution in cancer-related malnutrition loss.…”

Section: Malnutrition and Cancermentioning

confidence: 99%

Underlying Causes and Co-existence of Malnutrition and Infections: An Exceedingly Common Death Risk in Cancer

et al. 2022

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In nutrition science, malnutrition is a state of imbalance between intake and the needs of the organism, leading to metabolic changes, impaired physiological functions, and weight loss. Regardless of the countless efforts being taken and researched for years, the burden of malnutrition is still alarming and considered a significant agent of mortality across the globe. Around 45% of 12 million children deaths (0–5 years old) annually are due to malnutrition, mostly from developing countries. Malnutrition develops associations with other infections and leads to substantial clinical outcomes, such as mortality, more visits to hospitals, poor quality of life and physical frailty, and socioeconomic issues. Here, in this review, we intend to provide an overview of the current burden, underlying risk factors, and co-existence of malnutrition and other infections, such as cancer. Following the rising concern of the vicious interplay of malnutrition and other medical illnesses, we believed that this narrative review would highlight the need to re-make and re-define the future strategies by giving comprehensive and sustainable programs to alleviate poverty and combat the rampant infectious diseases and those nutrition-related health problems. Furthermore, the study also raises the concern for hospitalized malnourished cancer patients as it is crucially important to knowledge the caregiver healthcare staff for early interventions of providing nutritional support to delay or prevent the onset of malnutrition.

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“…The circadian clock maintains cellular homeostasis and systemic physiology (31)(32)(33). However, altered circadian gene expression signatures are associated with several diseases including multiple cancer types (34)(35)(36)(37)(38)(39)(40)(41)(42). Human data from The Cancer Genome Atlas (TCGA) show a significant correlation between a subset of deregulated core clock genes and oncogenic driver pathways, survival rates, and tumor staging in 32 different cancer types (43).…”

Section: Introductionmentioning

confidence: 99%

Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer

et al. 2022

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An alarming rise in young onset colorectal cancer (CRC) has been reported; however, the underlying molecular mechanism remains undefined. Suspected risk factors of young onset CRC include environmental aspects, such as lifestyle and dietary factors, which are known to affect the circadian clock. We find that both genetic disruption and environmental disruption of the circadian clock accelerate Apc- driven CRC pathogenesis in vivo. Using an intestinal organoid model, we demonstrate that clock disruption promotes transformation by driving Apc loss of heterozygosity, which hyperactivates Wnt signaling. This up-regulates c-Myc , a known Wnt target, which drives heightened glycolytic metabolism. Using patient-derived organoids, we show that circadian rhythms are lost in human tumors. Last, we identify that variance between core clock and Wnt pathway genes significantly predicts the survival of patients with CRC. Overall, our findings demonstrate a previously unidentified mechanistic link between clock disruption and CRC, which has important implications for young onset cancer prevention.

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Glucagon regulates the stability of REV-ERBα to modulate hepatic glucose production in a model of lung cancer–associated cachexia

Cited by 21 publications

References 78 publications

MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer

MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer

Underlying Causes and Co-existence of Malnutrition and Infections: An Exceedingly Common Death Risk in Cancer

Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer

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