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Abstract
Glioblastoma (GBM) is the most common and deadly of the primary intracranial tumors and is comprised of subsets that show plasticity and marked heterogeneity, contributing to the lack of success in genomic profiling to guide development of precision medicine for these tumors. In this study, a mutation in isocitrate dehydrogenase 1 was found to suppress the transforming growth factor-beta signaling pathway and E2F4 interacted with Smad3 to inhibit expression of mesenchymal markers. However, palmitoylation of Smad3 mediated by palmitoyltransferase ZDHHC19 promoted activation of the transforming growth factor-beta signaling pathway, and its interaction with EP300 promoted expression of mesenchymal markers in the mesenchymal subtype of GBM. Smad3 and hypoxia-inducible factor 1-alpha may be important molecular targets for treatment of glioma because they appear to coordinate the basic aspects of cancer stem cell biology.
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1 Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui 230031, China. MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Anhui Province Key Laboratory of Medical Physics and Technology, Hefei, China (GRID:grid.454811.d) (ISNI:0000 0004 1792 7603); University of Science and Technology of China, Hefei, China (GRID:grid.59053.3a) (ISNI:0000000121679639); The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Department of Anesthesiology, Hefei, China (GRID:grid.59053.3a) (ISNI:0000000121679639)
2 Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui 230031, China. MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Anhui Province Key Laboratory of Medical Physics and Technology, Hefei, China (GRID:grid.454811.d) (ISNI:0000 0004 1792 7603); University of Science and Technology of China, Hefei, China (GRID:grid.59053.3a) (ISNI:0000000121679639)
3 Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui 230031, China. MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Anhui Province Key Laboratory of Medical Physics and Technology, Hefei, China (GRID:grid.454811.d) (ISNI:0000 0004 1792 7603); The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Department of Anesthesiology, Hefei, China (GRID:grid.59053.3a) (ISNI:0000000121679639); Hefei Cancer Hospital, Chinese Academy of Sciences, Department of Laboratory Medicine, Hefei, China (GRID:grid.9227.e) (ISNI:0000000119573309)
4 Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui 230031, China. MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Anhui Province Key Laboratory of Medical Physics and Technology, Hefei, China (GRID:grid.454811.d) (ISNI:0000 0004 1792 7603); Hefei Cancer Hospital, Chinese Academy of Sciences, Department of Laboratory Medicine, Hefei, China (GRID:grid.9227.e) (ISNI:0000000119573309)