A5058432318- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Peroxisome Proliferator-Activated Receptors
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Autophagy in Disease and Therapy
- Cancer Research and Treatments
- Fibroblast Growth Factor Research
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Amino Acid Enzymes and Metabolism
- Protein Degradation and Inhibitors
- Diabetes Treatment and Management
- Adipose Tissue and Metabolism
- Drug Transport and Resistance Mechanisms
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Lung Cancer Treatments and Mutations
- Genetic Syndromes and Imprinting
- Parathyroid Disorders and Treatments
Tongji University
2020-2025
Tongji Hospital
2022-2025
Yuhuangding Hospital
2015-2024
Eli Lilly (United States)
2003-2024
University of North Carolina at Chapel Hill
2015-2022
Shanghai Jiao Tong University
2013-2022
Ruijin Hospital
2022
Qingdao University
2019
Affiliated Hospital of Qingdao University
2019
UNC Lineberger Comprehensive Cancer Center
2015-2019
The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified structural maintenance chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. infection degraded SMC5/6 in human hepatocytes vitro humanized mice vivo. targets ubiquitylation by subsequent...
Abstract Purpose: FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer therapeutic potential AZD4547, a potent selective ATP-competitive receptor tyrosine kinase inhibitor fibroblast factor (FGFR)1–3, patients FGFR2-amplified cancer. Experimental Design: Array-comparative genomic hybridization FISH were used to identify patient samples. The effects modulation investigated cells patient-derived xenograft (PDGCX)...
Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently hematopoietic malignancy, but rarely solid tumors which instead commonly have reduced activity. The impact of decreased activity is not known. Here we show that TET2 mediates interferon γ (IFNγ)-JAK-STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration cancer immunity. IFNγ stimulated STAT1 bind recruit hydroxymethylate genes. Reduced was associated with TH1-type chemokines...
A bstract Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) catalyzes generation of fructose-2,6-bisphosphate, a potent allosteric stimulator glycolysis. Intriguingly, among four members PFKFB family, PFKFB3 uniquely localized nucleus, reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which...
Significance PD-L1 is well known as an immune checkpoint molecule, which suppresses surveillance through binding to its receptor PD-1. Intracellular can also protect messenger RNAs of several DNA damage repair–related genes from degradation and enhance tumor resistance DNA-damaging therapy. Triple-negative breast cancer (TNBC) has the worst prognosis highest risk distant relapse in shows immunotherapy radiotherapy. In this study, we found that D-mannose promote significantly radiotherapy...
Abstract Purpose: To investigate the incidence of FGFR1 amplification in Chinese non–small cell lung cancer (NSCLC) and to preclinically test hypothesis that novel, potent, selective fibroblast growth factor receptor (FGFR) small-molecule inhibitor AZD4547 will deliver potent antitumor activity NSCLC FGFR1–amplified patient-derived tumor xenograft (PDTX) models. Experimental Design: A range assays was used assess translational relevance treatment including vitro line panel screening...
The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. TAZ functions as a transcriptional co-activator downstream of the has been implicated in human cancer development. A key step Hippo-TAZ is phosphorylation LATS kinase, which leads to inhibition cytoplasmic retention degradation. However, mechanism dephosphorylation responsible phosphatase are unknown. Here, we identified PP1 bona fide phosphatase. PP1A dephosphorylates at Ser-89 Ser-311, promotes...
Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis nucleotide precursors amino acids. Inhibition PGAM by small RNAi or molecule attenuates cell proliferation tumor growth. activity is commonly upregulated cells, but how regulated vivo remains poorly understood. Here we report that acetylated at lysine 100 (K100), active site residue invariably conserved from bacteria, to yeast,...
Gastric cancer (GC) is a leading cause of deaths worldwide. Since the approval trastuzumab, targeted therapies are emerging as promising treatment options for disease. This study aimed to explore molecular segmentation several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast (FGFR2), within GC using clinically approved or investigational kits scoring criteria. Knowledge how these markers segmented in same cohort patients could improve future...
Non-small-cell lung cancer patients with activating mutations in epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitor (TKI) treatment. Nevertheless, often develop central nervous system (CNS) metastases during treatment, even when their extracranial tumors are still under control. In the absence of effective options, much higher doses TKIs have been attempted clinically, goal achieving high enough drug concentrations within CNS. Although limited tumor responses...
How cancer cells evade the therapeutic effects of immune checkpoint blockade is largely unknown. Here, we report that fibrinogen-like protein 1 (FGL1), a newly identified ligand, was modified by acetylation at Lys 98 in hepatocellular carcinoma (HCC), which targeted it for proteasomal degradation. Sirtuin 2 (SIRT2) deacetylated and stabilized FGL1, thus promoting evasion. Notably, SIRT2 inhibitor 2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2) enhanced FGL1...
The altered metabolism in most tumor cells consists of elevated glucose uptake and increased glycolysis even the presence high oxygen tension. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an obligatory enzyme glycolysis. Here, we report that acetylation at lysine 254 (K254) increases GAPDH activity response to glucose. Furthermore, reversibly regulated by acetyltransferase PCAF deacetylase HDAC5. Substitution K254 glutamine compromises ability support cell proliferation growth. Our...
Activation of TGR5 via bile acids or acid analogs leads to the release glucagon-like peptide-1 (GLP-1) from intestine, increases energy expenditure in brown adipose tissue, and gallbladder filling with bile. Here, we present compound 18, a non-bile agonist that demonstrates robust GLP-1 secretion mouse enteroendocrine cell line yet weak human line. Acute administration 18 mice increased peptide YY (PYY) secretion, leading lowering glucose excursion an oral tolerance test (OGTT), while...
Bile acids are steroid-derived molecules synthesized in the liver, secreted from hepatocytes into bile canaliculi, and subsequently stored gall bladder. During feeding, flows duodenum, where it contributes to solubilization digestion of lipid-soluble nutrients. After a meal, bile-acid levels increase intestine, also systemic circulation. Therefore, serum serve as an important sensing mechanism for nutrient energy. Recent studies have described versatile signaling endowed with endocrine...
Abstract Inactivating mutations of von Hippel–Lindau (VHL) are highly prevalent in clear cell renal carcinoma (ccRCC). Improved understanding the vulnerabilities VHL-deficient ccRCC could lead to improved treatment strategies. The activity DNA dioxygenase ten-eleven translocation (TET)2 is significantly reduced multiple cancers by different mechanisms, but its role progression remains unclear. Here, we report that increased expression TET2, not TET1 and TET3, negatively associated with tumor...
Vitamin D plays critical role in the female reproductive system. It seems that vitamin is associated with clinical pregnancy outcomes of assisted technologies (ART), but its remains elusive. This study aimed to establish whether vitro fertilization (IVF). The cross-sectional was carried out from January 1st 2017 December 31st 2017. A total 848 patients who had indications for IVF were enrolled. classified by serum 25 (OH) quartiles. outcome parameters compared each group, including normal...
Abstract Clear cell renal carcinoma (ccRCC) is the most lethal subtype of cancer, and its treatment options remain limited. Therefore, there an urgent need to discover therapeutic agents for ccRCC treatment. Here, we demonstrate that dimethyl fumarate (DMF), approved medication multiple sclerosis [1] psoriasis, can inhibit proliferation cells. Mechanistically, hepatocyte nuclear factor 1β (HNF1B), a transcription highly expressed in ccRCC, succinated by DMF at cysteine residues, leading...