2020
DOI: 10.1016/j.isci.2020.100839
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A Non-canonical Function of BMAL1 Metabolically Limits Obesity-Promoted Triple-Negative Breast Cancer

Abstract: Circadian regulator BMAL1 rewires metabolism in a chronic insulin-treated TNBC model Pyruvate links BMAL1 to mitochondrial bioenergetics BMAL1 suppresses tumor proliferation and metastasis in hyperinsulinemic obese mice BMAL1 influences tumor microenvironment in highfat-diet-fed mice

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Cited by 26 publications
(24 citation statements)
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References 83 publications
(74 reference statements)
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“…Among canonical clock genes, only BMAL1 knockout results in complete loss of circadian rhythm in both SCN and peripheral tissues [ 14 ], which certificates the key role of BMAL1 in the circadian system. Studies revealed that BMAL1 is involved in the pathogenesis of human cancers, functioning either as tumor suppressor or oncogenic factor [ 15 , 16 , 17 , 18 ]. Although BMAL1 exhibits a globally repressive function in many tumors, a high level of BMAL1 and CLOCK expressions are often associated with poorly differentiated or late-stage CRC as well as liver metastasis [ 19 , 20 ].…”
Section: Introductionmentioning
confidence: 99%
“…Among canonical clock genes, only BMAL1 knockout results in complete loss of circadian rhythm in both SCN and peripheral tissues [ 14 ], which certificates the key role of BMAL1 in the circadian system. Studies revealed that BMAL1 is involved in the pathogenesis of human cancers, functioning either as tumor suppressor or oncogenic factor [ 15 , 16 , 17 , 18 ]. Although BMAL1 exhibits a globally repressive function in many tumors, a high level of BMAL1 and CLOCK expressions are often associated with poorly differentiated or late-stage CRC as well as liver metastasis [ 19 , 20 ].…”
Section: Introductionmentioning
confidence: 99%
“…is consistently associated with increased risk of metastasis (Ramos et al, 2020). Similarly, pancreatic cancer cells are reported to have less BMAL1 than non-cancerous controls (Jiang et al, 2016).…”
Section: Bmal1mentioning
confidence: 98%
“…Moreover, the depletion of ARG2 causes ammonia accumulation and suppresses PDAC, particularly in obese hosts [ 94 ]. In a search for mechanisms underlying the increased cancer risk that is associated with the combination of metabolic deregulation and circadian disruption, Ramos et al demonstrated that a non-canonical function of BMAL1 limits obesity-promoted triple-negative breast cancer [ 95 ]. BMAL1, a key circadian transcription factor, suppresses the flexibility of mitochondrial substrate usage and pyruvate-dependent mitochondrial respiration induced by chronic insulin treatment in vitro .…”
Section: Molecular Mechanisms Of the Obesity-cancer Connectionmentioning
confidence: 99%
“…Interestingly, orthotopic transplantation of E0771 breast cancer cells depleted for BMAL1 revealed that BMAL1 functions as a tumor suppressor in obese, but not in lean mice. In humans, down-regulation of BMAL1 is associated with higher risk of metastasis [ 95 ].…”
Section: Molecular Mechanisms Of the Obesity-cancer Connectionmentioning
confidence: 99%