| http://purl.uniprot.org/citations/33990700 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33990700 | http://www.w3.org/2000/01/rdf-schema#comment | "5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2-p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41388-021-01815-4"xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Chen C."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Liu X."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Lu H."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Song G."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Tang H."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Zhuang G."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Na R."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Fan G."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Xiao C."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Yan D."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Peng Z."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/author | "Chen J.'"xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/pages | "3974-3988"xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/title | "The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy."xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://purl.uniprot.org/core/volume | "40"xsd:string |
| http://purl.uniprot.org/citations/33990700 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33990700 |
| http://purl.uniprot.org/citations/33990700 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33990700 |