| http://purl.uniprot.org/citations/31519767 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31519767 | http://www.w3.org/2000/01/rdf-schema#comment | "Tamoxifen has been clinically used in treating estrogen receptor (ER)-positive breast cancer for over 30 years. The most challenging aspect associated with tamoxifen therapy is the development of resistance in initially responsive breast tumors. We applied a parallel-reaction monitoring (PRM)-based quantitative proteomic method to examine the differential expression of kinase proteins in MCF-7 and the isogenic tamoxifen-resistant (TamR) cells. We were able to quantify the relative protein expression levels of 315 kinases, among which hexokinase 2 (HK2) and mTOR were up-regulated in TamR MCF-7 cells. We also observed that the TamR MCF-7 cells exhibited elevated rate of glycolysis than the parental MCF-7 cells. In addition, we found that phosphorylation of S6K - a target of mTOR - was much lower in TamR MCF-7 cells, and this phosphorylation level could be restored upon genetic depletion or pharmacological inhibition of HK2. Reciprocally, the level of S6K phosphorylation was diminished upon overexpression of HK2 in MCF-7 cells. Moreover, we observed that HK2 interacts with mTOR, and this interaction inhibits mTOR activity. Lower mTOR activity led to augmented autophagy, which conferred resistance of MCF-7 cells toward tamoxifen. Together, our study demonstrates that elevated expression of HK2 promotes autophagy through inhibiting the mTOR-S6K signaling pathway and results in resistance of MCF-7 breast cancer cells toward tamoxifen; thus, our results uncovered, for the first time, HK2 as a potential therapeutic target for overcoming tamoxifen resistance."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.org/dc/terms/identifier | "doi:10.1074/mcp.ra119.001576"xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Dai X."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Liu X."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Huang M."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/author | "Miao W."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/name | "Mol Cell Proteomics"xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/pages | "2273-2284"xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/title | "Elevated Hexokinase II Expression Confers Acquired Resistance to 4-Hydroxytamoxifen in Breast Cancer Cells."xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://purl.uniprot.org/core/volume | "18"xsd:string |
| http://purl.uniprot.org/citations/31519767 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31519767 |
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