Publications

Detailed Information

Dopamine receptor D2 regulates glioblastoma survival and death through MET and death receptor 4/5

Cited 8 time in Web of Science Cited 8 time in Scopus
Authors

Jeon, Hye-Min; Oh, Young Taek; Shin, Yong Jae; Chang, Nakho; Kim, Donggeun; Woo, Donghun; Yeup, Yoon; Joo, Kyeung Min; Jo, Heejin; Yang, Heekyoung; Lee, Jin-Ku; Kang, Wonyoung; Sa, Jason; Lee, Won Jun; Hale, James; Lathia, Justin D.; Purow, Benjamin; Park, Myung Jin; Park, Jong Bae; Nam, Do-Hyun; Lee, Jeongwu

Issue Date
2023-05
Publisher
Elsevier BV
Citation
Neoplasia, Vol.39, p. 100894
Abstract
Recent studies indicate that signaling molecules traditionally associated with central nervous system function play critical roles in cancer. Dopamine receptor signaling is implicated in various cancers including glioblastoma (GBM) and it is a recognized therapeutic target, as evidenced by recent clinical trials with a selective dopamine receptor D2 (DRD2) inhibitor ONC201. Understanding the molecular mechanism(s) of the dopamine receptor signaling will be critical for development of potent therapeutic options. Using the human GBM patient-derived tumors treated with dopamine receptor agonists and antagonists, we identified the proteins that interact with DRD2. DRD2 signaling promotes glioblastoma (GBM) stem-like cells and GBM growth by activating MET. In contrast, pharmacological inhibition of DRD2 induces DRD2-TRAIL receptor interaction and subsequent cell death. Thus, our findings demonstrate a molecular circuitry of oncogenic DRD2 signaling in which MET and TRAIL receptors, critical factors for tumor cell survival and cell death, respectively, govern GBM survival and death. Finally, tumor-derived dopamine and expression of dopamine biosynthesis enzymes in a subset of GBM may guide patient stratification for DRD2 targeting therapy.
ISSN
1522-8002
URI
https://hdl.handle.net/10371/191538
DOI
https://doi.org/10.1016/j.neo.2023.100894
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Related Researcher

  • College of Medicine
  • Department of Medicine
Research Area 3D drug screening, Cancer Organoid, Precision Oncologuy

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share