A5077605764- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer Immunotherapy and Biomarkers
- Head and Neck Cancer Studies
- Autophagy in Disease and Therapy
- Cancer Diagnosis and Treatment
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Caveolin-1 and cellular processes
- Hematopoietic Stem Cell Transplantation
- Cancer-related Molecular Pathways
- Diet and metabolism studies
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Acute Lymphoblastic Leukemia research
- Cancer Genomics and Diagnostics
- Viral-associated cancers and disorders
- ATP Synthase and ATPases Research
- Metabolomics and Mass Spectrometry Studies
- CAR-T cell therapy research
- Sarcoma Diagnosis and Treatment
Sidney Kimmel Cancer Center
2016-2025
Thomas Jefferson University
2016-2025
Sidney Kimmel Comprehensive Cancer Center
2025
Thomas Jefferson University Hospital
2013-2024
Jefferson University Hospitals
2023-2024
Albert Einstein College of Medicine
2021
Wellcome Centre for Mitochondrial Research
2021
National and Kapodistrian University of Athens
2018
Philadelphia University
2010-2013
Institute for Stem Cell Biology and Regenerative Medicine
2011-2012
Here, we propose a new model for understanding the Warburg effect in tumor metabolism. Our hypothesis is that epithelial cancer cells induce (aerobic glycolysis) neighboring stromal fibroblasts. These cancer-associated fibroblasts, then undergo myo-fibroblastic differentiation, and secrete lactate pyruvate (energy metabolites resulting from aerobic glycolysis). Epithelial could take up these energy-rich use them mitochondrial TCA cycle, thereby promoting efficient energy production (ATP...
Previously, we proposed a new model for understanding the "Warburg effect" in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter TCA cycle, high ATP production via oxidative phosphorylation. We have termed paradigm "The Reverse Warburg Effect." Here, directly evaluate whether end-products of (3-hydroxy-butyrate L-lactate) can stimulate growth...
Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor poor prognosis in human breast cancer patients, and associated with early tumor recurrence, lymph node metastasis, tamoxifen-resistance. We developed novel co-culture system to understand the mechanism(s) by which loss Cav-1 induces "lethal micro-environment". Here, we propose new paradigm explain prognostic value Cav-1. In this model, cells induce oxidative stress fibroblasts, then acts as "metabolic"...
// Rebecca Lamb 1,2,* , Bela Ozsvari Camilla L. Lisanti 3,** Herbert B. Tanowitz 4 Anthony Howell 1,2 Ubaldo E. Martinez-Outschoorn 5 Federica Sotgia and Michael P. 1 The Breakthrough Breast Cancer Research Unit, Institute of Sciences, University Manchester, UK 2 Manchester Centre for Cellular Metabolism (MCCM), 3 Moor Allerton Preparatory School, Didsbury, Departments Pathology Medicine, Albert Einstein College Bronx, NY, USA Kimmel Center, Philadelphia, PA, * These authors contributed...
Recently, using a co-culture system, we demonstrated that MCF7 epithelial cancer cells induce oxidative stress in adjacent cancer-associated fibroblasts, resulting the autophagic/lysosomal degradation of stromal caveolin-1 (Cav-1). However, detailed signaling mechanism(s) underlying this process remain largely unknown. Here, show hypoxia is sufficient to autophagic Cav-1 which blocked by lysosomal inhibitor chloroquine. Concomitant with hypoxia-induced Cav-1, see upregulation number...
Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to “feed” adjacent cells, which then drives mitochondrial biogenesis oxidative metabolism cells. Thus, there is vectorial transport of energy-rich substrates from fibroblastic tumor stroma anabolic A prediction hypothesis that should express MCT4, mono-carboxylate transporter has been implicated efflux...
Previously, we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth experimental metastasis in an vivo xenograft model, most likely by driving oxidative mitochondrial metabolism breast cancer cells. To mechanistically understand how these affect cell behavior, here used genome-wide transcriptional profiling. Briefly, human cells (MCF7) were cultured with lactate or ketones, then subjected to analysis (exon-array). Interestingly, our results show treatment increases...
We have previously shown that a loss of stromal Cav-1 is biomarker poor prognosis in breast cancers. Mechanistically, induces the metabolic reprogramming cells, with increased autophagy/mitophagy, mitochondrial dysfunction and aerobic glycolysis. As consequence, Cav-1-low CAFs generate nutrients (such as L-lactate) chemical building blocks fuel metabolism anabolic growth adjacent cancer cells. It also known associated hyperactive TGF-β signaling. However, it remains unknown whether...
We have recently proposed a new mechanism for explaining energy transfer in cancer metabolism. In this scenario, cells behave as metabolic parasites, by extracting nutrients from normal host cells, such fibroblasts, via the secretion of hydrogen peroxide initial trigger. Oxidative stress tumor microenvironment then leads to autophagy-driven catabolism, mitochondrial dys-function, and aerobic glycolysis. This, turn, produces high-energy (such L-lactate, ketones, glutamine) that drive anabolic...
Previously, we proposed that cancer cells behave as metabolic parasites, they use targeted oxidative stress a "weapon" to extract recycled nutrients from adjacent stromal cells. Oxidative in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting compartmentalized cellular catabolism, loss of mitochondrial function, the onset aerobic glycolysis, tumor stroma. As such, produce high-energy (such lactate ketones) fuel biogenesis, metabolism We have termed this new...
We have recently proposed a new model of cancer metabolism to explain the role aerobic glycolysis and L-lactate production in fueling tumor growth metastasis. In this model, cells secrete hydrogen peroxide (H2O2), initiating oxidative stress stroma. This, turn, drives secretion from cancer-associated fibroblasts. Secreted then fuels mitochondrial (OXPHOS) epithelial cells, by acting as paracrine onco-metabolite. previously termed type two-compartment "Reverse Warburg Effect," takes place...
Here, we show that new mitochondrial biogenesis is required for the anchorage independent survival and propagation of cancer stem-like cells (CSCs). More specifically, used drug XCT790 as an investigational tool, it functions a specific inhibitor ERRα-PGC1 signaling pathway, which governs biogenesis. Interestingly, our results directly demonstrate efficiently blocks both tumor initiating (TICs), using MCF7 cell line model system. Mechanistically, suppresses activity several pathways are...
Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with onset of senescence. Thus, and senescence may be part same physiological process, as autophagy-senescence transition (AST). To test this hypothesis, human immortalized telomerase (hTERT-BJ1) were stably transfected genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient induce a constitutive autophagic...
Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed determine the state proliferative cells. Interestingly, cell proliferation cells, as marked by Ki-67 immunostaining, strictly correlated with oxidative mitochondrial metabolism (OXPHOS) uptake fuels, detected via MCT1 expression (p < 0.001). More specifically, three...
Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage for treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis immune-compromised patients. a hydroxy-1,4-naphthoquinone analogue ubiquinone, also known as Co-enzyme Q10 (CoQ10). It well-tolerated drug that does not cause myelo-suppression. Mechanistically, it thought to act potent and selective OXPHOS inhibitor, by targeting CoQ10-dependence mitochondrial...