Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG
Hannah E. Wilson,David A. Stanton,Stephanie L. Rellick,Werner J. Geldenhuys,Emidio E. Pistilli +4 more
TLDR
In this article, the authors investigated alterations induced in skeletal muscle by BC-derived factors in an in vitro conditioned media (CM) system and tested the hypothesis that BC cells secrete a factor that represses PPARγ (PPARG) expression and its transcriptional activity, leading to downregulation of PPARG target genes involved in mitochondrial function and other metabolic pathways.Abstract:
The peroxisome proliferator-activated receptors (PPARs) have been previously implicated in the pathophysiology of skeletal muscle dysfunction in women with breast cancer (BC) and animal models of BC. This study investigated alterations induced in skeletal muscle by BC-derived factors in an in vitro conditioned media (CM) system and tested the hypothesis that BC cells secrete a factor that represses PPAR-γ (PPARG) expression and its transcriptional activity, leading to downregulation of PPARG target genes involved in mitochondrial function and other metabolic pathways. We found that BC-derived factors repress PPAR-mediated transcriptional activity without altering protein expression of PPARG. Furthermore, we show that BC-derived factors induce significant alterations in skeletal muscle mitochondrial function and lipid accumulation, which are rescued with exogenous expression of PPARG. The PPARG agonist drug rosiglitazone was able to rescue BC-induced lipid accumulation but did not rescue effects of BC-derived factors on PPAR-mediated transcription or mitochondrial function. These data suggest that BC-derived factors alter lipid accumulation and mitochondrial function via different mechanisms that are both related to PPARG signaling, with mitochondrial dysfunction likely being altered via repression of PPAR-mediated transcription, and lipid accumulation being altered via transcription-independent functions of PPARG.read more
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Chemotherapy impairs skeletal muscle mitochondrial homeostasis in early breast cancer patients
Joris Mallard,Elyse Hucteau,Anne-Laure Charles,Laura Bender,Claire Baeza,Mathilde Pélissié,Philippe Trensz,C. Pflumio,Michal Kalish-Weindling,Bernard Geny,Roland Schott,Fabrice Favret,Xavier Pivot,Thomas J. Hureau,Allan F. Pagano +14 more
TL;DR: Investigation of overall skeletal muscle mitochondrial homeostasis in early breast cancer patients undergoing chemotherapy, including mitochondrial quantity, function, and dynamics finds abnormalities in both quantity and function.
Journal ArticleDOI
Skeletal Muscle Deconditioning in Breast Cancer Patients Undergoing Chemotherapy: Current Knowledge and Insights From Other Cancers.
TL;DR: In this article, a review of recent advances in both macroscopic changes and cellular mechanisms implicated in skeletal muscle deconditioning of breast cancer patients, particularly as a consequence of the chemotherapy treatment, is presented.
Journal ArticleDOI
A New Approach to Understanding Cancer-Related Fatigue: Leveraging the 3P Model to Facilitate Risk Prediction and Clinical Care
Alix G. Sleight,Sylvia L. Crowder,Jacek Skarbinski,Paul M Coen,Nathan H. Parker,Aasha I. Hoogland,Brian D. Gonzalez,Mary C. Playdon,Steven Douglas Cole,Jennifer Ose,Yuichi Murayama,Erin M. Siegel,Jane C. Figueiredo,Heather S. L. Jim +13 more
TL;DR: It is proposed that the 3P model may be leveraged—particularly using metabolomics, the microbiome, and inflammation in conjunction with behavioral science—to better understand the pathophysiology of cancer-related fatigue.
Journal ArticleDOI
Development and Validation of a Novel PPAR Signaling Pathway-Related Predictive Model to Predict Prognosis in Breast Cancer
Yingkun Xu,Danhua Shu,Mei-Chen Shen,Qiulin Wu,Yang Peng,Li Liu,Zhenrong Tang,Shun Gao,Yan Wang,Shengchun Liu +9 more
TL;DR: This study conducted a preliminary screening of genes related to the PPAR signaling pathway through univariate Cox analysis, then used LASSO regression analysis to conduct a second screening, and successfully established a risk model consisting of ten genes in BRCA, a novel prognostic-related risk model.
Journal ArticleDOI
[Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study].
TL;DR: HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1, which might be the most important target for HQSJzD to treat CRF.
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