PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src.

Autor: Yang Y; Department of Immunology, School of Basic Medicine, Qingdao University, 16 Jiangsu Road, Qingdao, 266071, PR China. Electronic address: yangyy1201@qdu.edu.cn., Tang N; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, 266021, PR China. Electronic address: tangningning1234@163.com., Liu Y; Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, PR China. Electronic address: swallow2309@qq.com., Choi W; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: chwoo1028@naver.com., Kim JH; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: kjhkjhmlml@skku.edu., Kim HG; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: hanks523@skku.edu., Yu T; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, 266021, PR China. Electronic address: yutao0112@qdu.edu.cn., Cho JY; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: jaecho@skku.edu.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Nov 01; Vol. 403, pp. 111252. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1016/j.cbi.2024.111252
Abstrakt: Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.
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 © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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