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

Autor:	Jeon HM; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Oh YT; Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea., Shin YJ; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Chang N; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Kim D; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Woo D; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Yeup Y; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Joo KM; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Jo H; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Yang H; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Lee JK; Department of Biomedical Sciences, Department of Anatomy and Cell Biology, Seoul National University, College of Medicine, Seoul, Republic of Korea., Kang W; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Sa J; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Lee WJ; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Hale J; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Lathia JD; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Purow B; Departments of Neurology, University of Virginia, Charlottesville, VA 22908, USA., Park MJ; Divisions of Radiation Cancer Research, Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea., Park JB; Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea., Nam DH; Cancer Stem Cell Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea., Lee J; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: leej7@ccf.org.
Jazyk:	angličtina
Zdroj:	Neoplasia (New York, N.Y.) [Neoplasia] 2023 May; Vol. 39, pp. 100894. Date of Electronic Publication: 2023 Mar 25.
DOI:	10.1016/j.neo.2023.100894
Abstrakt:	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. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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