Vitamin C functions as double-edge sword on cancer progression depending on ERK activation or inhibition mediated by its receptor SVCT2
Guan, Y.; Chen, B.; Wu, Y.; Han, Z.; Xu, H.; Zhang, C.; Hao, W.; Gao, W.; Guo, Z.
Show abstract
The effect of Vitamin C (Vc) in oncotherapy was controversial for decades. And hyperactivation of extracellular signal-regulated kinase (ERK) drove tumorigenesis. Herein, we demonstrated that Vc activated ERK through sodium-dependent Vc transporter 2 (SVCT2), while high-dose Vc resulted in persistent ERK feedback inhibition following activation. Extracellular Vc binding to SVCT2 initiated ERK activation, then transmembrane transport of Vc induced dimerization of SVCT2. Activated ERK phosphorylated protein tyrosine phosphatase non-receptor type 12 (PTPN12) at Ser434 and inhibited PTPN12 activity, thus enhancing phosphorylation of Janus kinase 2 (JAK2), which phosphorylated growth factor receptor bound protein 2 (GRB2) at Tyr160 to promote GRB2 dimers dissociation and recruitment of GRB2 to SVCT2, leading to further ERK activation. Different cancers have different sensitivities to Vc, the dose effects of Vc on cancer phenotypes depended on that ERK was activated or inhibited. These findings suggest SVCT2 is a Vc receptor mediating the ERK-PTPN12-JAK2-GRB2-ERK positive feedback loop and a potential target for oncotherapy. Abstract graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/475954v2_ufig1.gif" ALT="Figure 1"> View larger version (72K): org.highwire.dtl.DTLVardef@9f75e7org.highwire.dtl.DTLVardef@f5bc18org.highwire.dtl.DTLVardef@10fe4c4org.highwire.dtl.DTLVardef@742b7d_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- TAK1-mediated phosphorylation of PLCE1 represses PIP2 hydrolysis to impede esophageal squamous cancer metastasis 96%
- TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1alpha axis in melanoma 95%
- STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer 95%
Similar papers in this journal
- Characterization of the Mechanisms Underlying Sulfasalazine-Induced Ferroptotic Cell Death: Role of Protein Disulfide Isomerase-Mediated NOS Activation and NO Accumulation 91%
- A pseudovirus-based method to dynamically mimic SARS-CoV-2-associated cell-to-cell fusion and transmission 91%
- Insulin-Induced Conformational Changes in the Full-Length Insulin Receptor: Structural Insights Gained from Molecular Modeling Analyses 90%
Similar papers in this journal
- Tumor cell-specific loss of GPX4 reprograms triacylglycerol metabolism to escape ferroptosis and impair antitumor immunity in NSCLC 92%
- Oxidative phosphorylation safeguards pluripotency via UDP-N-acetylglucosamine 92%
- Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 91%
Similar papers in this journal
- Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development 94%
- SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury 93%
- ACE2-Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker 92%
Similar papers in this journal
- Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD 92%
- Pyroptosis of syncytia formed by fusion of SARS-CoV-2 Spike and ACE2 expressing cells 92%
- Metabolic control of histone acetylation for precise and timely regulation of minor ZGA in early mammalian embryos 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.