Metabolic Reprogramming and Dependencies Associated with Epithelial Cancer Stem Cells Independent of the Epithelial-Mesenchymal Transition Program. | LitMetric
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Diagonal 643, Barcelona, Spain.
Published: May 2016
AI Article Synopsis
Article Abstract
In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analyses that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics, and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis. Stem Cells 2016;34:1163-1176.
Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies due to their self-renewal and differentiation capabilities. Pathological microenvironments expose MSCs to senescence-inducing factors such as reactive oxygen species (ROS), resulting in MSC functional decline and loss of stemness. Oxidative stress leads to mitochondrial dysfunction, a hallmark of senescence, and is prevalent in aging tissues characterized by elevated ROS levels.
Undifferentiated pleomorphic sarcoma, an exceedingly rare and aggressive primary cardiac tumor arising from mesenchymal stem cells, is associated with poor prognosis and high mortality despite adequate treatment. A 52-year-old female presented with a 2-month history of angina and dyspnea on exertion. Her clinical history included severe acute respiratory syndrome coronavirus 2 myocarditis and iron deficiency anemia.
Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Human immunodeficiency Virus (HIV) and () co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/ co-infection is complex and challenging. CD8T cells play a pivotal role in the adaptive immune response to both HIV and .
State Key Laboratory of Trauma and Chemical Poisoning, Department of Stem Cell and Regenerative Medicine, Daping Hospital, Army Medical University, Chongqing, China.
Background: To determine the role of N-methyladenosine (mA) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).
Methods: Consensus clustering was performed to identify the subgroups with distinct immune or mA modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays.
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France.
Hematopoietic stem cells (HSCs) are a rare, long-lived and multipotent population that give rise to majority of blood cells and some tissue-resident immune cells. There is growing evidence that inflammatory stimuli can trigger persistent reprogramming in HSCs that enhances or inhibits the cellular functions of these HSCs and their progeny in response to subsequent infections. This newly discovered property makes HSCs a reservoir for innate immune memory.
