A5050158990- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Neuroblastoma Research and Treatments
- ATP Synthase and ATPases Research
- Biotin and Related Studies
- Electrochemical sensors and biosensors
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Metabolism, Diabetes, and Cancer
- Salivary Gland Disorders and Functions
- Glioma Diagnosis and Treatment
- Mesenchymal stem cell research
- Immune cells in cancer
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Metabolomics and Mass Spectrometry Studies
- High Altitude and Hypoxia
Shandong University
2024
Shandong First Medical University
2024
Shandong Tumor Hospital
2024
Stanford University
2019-2024
Agilent Technologies (Germany)
2024
University of California, San Diego
2024
Weatherford College
2023
Stanford Medicine
2021-2022
Zhongda Hospital Southeast University
2017
Loss of the von Hippel-Lindau (VHL) tumor suppressor is a hallmark feature renal clear cell carcinoma. VHL inactivation results in constitutive activation hypoxia-inducible factors (HIFs) HIF-1 and HIF-2 their downstream targets, including proangiogenic VEGF PDGF. However, antiangiogenic agents inhibitors have limited efficacy cancer therapy due to development resistance. Here we employed an innovative computational platform, Mining Synthetic Lethals (MiSL), identify synthetic lethal...
Immunotherapy, especially immune checkpoint inhibitors, has revolutionized clinical practice within the last decade. However, primary and secondary resistance to immunotherapy is common in patients with diverse types of cancer. It well-acknowledged that tumor cells can facilitate formation immunosuppressive microenvironments via metabolism reprogramming, lactic acid, metabolite glycolysis, a significant contributor. SLC16A3 (also named as MCT4) transporter mediating acid efflux. In this...
Despite the fact that Otto H. Warburg discovered effect almost one hundred years ago, why cancer cells waste most of glucose carbon as lactate remains an enigma. proposed a connection between and cell dedifferentiation. Hypoxia is common tumor microenvironmental stress induces blocks differentiation. The underlying mechanism by which this occurs poorly understood, no effective therapeutic strategy has been developed to overcome resistance Using neuroblastoma differentiation model, we hypoxia...
Abstract The Warburg effect is the major metabolic hallmark of cancer. According to himself, consequence cell dedifferentiation. Therefore, reversing might be an approach restore differentiation in In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), activate respiration, which induced neural neuroblastoma cells. NEN treatment increased NAD+/NADH and pyruvate/lactate ratios also α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, promoter CpG island...
Loss of estrogen receptor (ER) pathway activity promotes breast cancer progression, yet how this occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in cancer, represses alpha (ERα) signaling by reprogramming glucose metabolism and epigenetics. Using isotope tracing time-resolved metabolomic analyses, demonstrate is required to maintain flux through glycolysis the TCA cycle support acetyl-CoA generation for histone acetylation. Consequently,...
Background Intermittent hypoxia (IH) induced by obstructive sleep apnea is the key factor involved in cardiovascular fibrosis. Under persistent condition, endothelial cells respond endothelial‐to‐mesenchymal transition (EndMT), which associated with Prolyl 4‐hydroxylase domain protein 3 (PHD3) a cellular oxygen sensor and its expression increased hypoxia. However, role apnea–induced EndMT fibrosis still uncertain. We investigated potential mechanism of cardiac perivascular PHD3 it. Methods...
Abstract When the electron transport chain (ETC) function is impaired, cancer cells rely on reductive carboxylation (RC) to convert α-ketoglutarate (αKG) citrate for macromolecular synthesis, thereby promoting tumor growth. Currently, there no viable therapy inhibit RC treatment. In this study, we demonstrate that mitochondrial uncoupler treatment effectively inhibits in cells. Mitochondrial activates ETC and increases NAD+/NADH ratio. Using U–13C-glutamine 1–13C-glutamine tracers, show...
<title>Abstract</title> Reduced mitochondrial quality and quantity in tumors is associated with dedifferentiation increased malignancy. However, it remains unclear how to restore tumors, whether restoration can drive tumor differentiation. Our study shows that restoring function using retinoic acid (RA) boost biogenesis a uncoupler enhance respiration synergistically drives neuroblastoma differentiation inhibits proliferation. U-<sup>13</sup>C-glucose/glutamine isotope tracing revealed...
Abstract Adult salivary stem/progenitor cells (SSPC) have an intrinsic property to self-renew in order maintain tissue architecture and homeostasis. glands been documented harbor SSPC, which shown play a vital role the regeneration of glandular structures postradiation damage. We previously demonstrated that activation aldehyde dehydrogenase 3A1 (ALDH3A1) after radiation reduced accumulation leading less apoptosis improved function. subsequently found sustained pharmacological ALDH3A1 is...
Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates neural crest with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram...
One-Sentence Summary Raf1 is present within the mitochondrial matrix, where it binds GLS to regulate glutamine catabolism and tumorigenesis. In cancer, activation occurs via mechanisms that include mutation of upstream regulators, such as receptor tyrosine kinases Ras GTPases, well by mutations affect RAF1 itself, including gene amplification ( 1 – 4 ). Once recruited plasma membrane PM ) can engage downstream mitogen-activated protein kinase MAPK pathway signaling through phosphorylation...
<p>S4. Mitochondrial uncoupler NEN inhibits reductive carboxylation under hypoxia.</p>
<p>S8. Mitochondrial uncoupling inhibits proliferation upon anchorage-independent growth.</p>
<p>S5. Mitochondrial uncoupler NEN, FCCP and BAM15 inhibit reductive carboxylation under hypoxia.</p>
<p>S9. ETC inhibition only inhibits proliferation, but not spheroid formation, while Mitochondrial uncoupling both.</p>
<p>S2. Mitochondrial uncoupler NEN accelerates forward TCA cycle and inhibits reductive carboxylation.</p>
<p>S6. Mitochondrial uncoupling inhibits reductive carboxylation in ccRCC cells.</p>
<p>S7. Mitochondrial uncoupling inhibits reductive carboxylation in spheroid culture.</p>
<p>S3. Mitochondrial uncoupler FCCP and BAM5 inhibit reductive carboxylation.</p>
<p>S1. Mitochondrial uncoupler NEN increases cellular NAD+/NADH ratio and inhibits reductive carboxylation.</p>
<div>Abstract<p>When the electron transport chain (ETC) function is impaired, cancer cells rely on reductive carboxylation (RC) to convert α-ketoglutarate (αKG) citrate for macromolecular synthesis, thereby promoting tumor growth. Currently, there no viable therapy inhibit RC treatment. In this study, we demonstrate that mitochondrial uncoupler treatment effectively inhibits in cells. Mitochondrial activates ETC and increases NAD+/NADH ratio. Using U-13C-glutamine 1-13C-glutamine...
<p>S9. ETC inhibition only inhibits proliferation, but not spheroid formation, while Mitochondrial uncoupling both.</p>
<p>S1. Mitochondrial uncoupler NEN increases cellular NAD+/NADH ratio and inhibits reductive carboxylation.</p>
<p>S8. Mitochondrial uncoupling inhibits proliferation upon anchorage-independent growth.</p>
<p>S3. Mitochondrial uncoupler FCCP and BAM5 inhibit reductive carboxylation.</p>