Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia
Summary: Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle was...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004607 |
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| author | Jeremy B. Ducharme Daria Neyroud Martin M. Schonk Miguel A. Gutierrez-Monreal Zhiguang Huo Haley O. Tucker Karyn A. Esser Sarah M. Judge Andrew R. Judge |
| author_facet | Jeremy B. Ducharme Daria Neyroud Martin M. Schonk Miguel A. Gutierrez-Monreal Zhiguang Huo Haley O. Tucker Karyn A. Esser Sarah M. Judge Andrew R. Judge |
| author_sort | Jeremy B. Ducharme |
| collection | DOAJ |
| description | Summary: Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal-muscle clock in response to cancer that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal-muscle circadian transcriptome toward pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal-muscle circadian transcriptome, which may contribute to muscle wasting and the development of cachexia. |
| format | Article |
| id | doaj-art-82d9d634afaf4a6dbf05ce50e091875f |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-82d9d634afaf4a6dbf05ce50e091875f2025-08-20T03:09:16ZengElsevierCell Reports2211-12472025-05-0144511568910.1016/j.celrep.2025.115689Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexiaJeremy B. Ducharme0Daria Neyroud1Martin M. Schonk2Miguel A. Gutierrez-Monreal3Zhiguang Huo4Haley O. Tucker5Karyn A. Esser6Sarah M. Judge7Andrew R. Judge8Department of Physical Therapy, University of Florida, Gainesville, FL, USA; Myology Institute, University of Florida, Gainesville, FL, USA; University of Florida Health Cancer Center, Gainesville, FL, USADepartment of Physical Therapy, University of Florida, Gainesville, FL, USA; Myology Institute, University of Florida, Gainesville, FL, USADepartment of Physical Therapy, University of Florida, Gainesville, FL, USA; Myology Institute, University of Florida, Gainesville, FL, USAMyology Institute, University of Florida, Gainesville, FL, USA; Department of Physiology and Aging, University of Florida, Gainesville, FL, USADepartment of Biostatistics, University of Florida, Gainesville, FL, USADepartment of Molecular Biosciences and the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USAMyology Institute, University of Florida, Gainesville, FL, USA; Department of Physiology and Aging, University of Florida, Gainesville, FL, USADepartment of Physical Therapy, University of Florida, Gainesville, FL, USA; Myology Institute, University of Florida, Gainesville, FL, USA; University of Florida Health Cancer Center, Gainesville, FL, USA; Corresponding authorDepartment of Physical Therapy, University of Florida, Gainesville, FL, USA; Myology Institute, University of Florida, Gainesville, FL, USA; University of Florida Health Cancer Center, Gainesville, FL, USA; Corresponding authorSummary: Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal-muscle clock in response to cancer that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal-muscle circadian transcriptome toward pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal-muscle circadian transcriptome, which may contribute to muscle wasting and the development of cachexia.http://www.sciencedirect.com/science/article/pii/S2211124725004607CP: Cancer |
| spellingShingle | Jeremy B. Ducharme Daria Neyroud Martin M. Schonk Miguel A. Gutierrez-Monreal Zhiguang Huo Haley O. Tucker Karyn A. Esser Sarah M. Judge Andrew R. Judge Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia Cell Reports CP: Cancer |
| title | Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia |
| title_full | Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia |
| title_fullStr | Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia |
| title_full_unstemmed | Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia |
| title_short | Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia |
| title_sort | cancer induced foxp1 disrupts and reprograms skeletal muscle circadian transcription in cachexia |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004607 |
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