Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation

Xiaoqing Fan; Junqi Fan; Haoran Yang; Chenggang Zhao; Wanxiang Niu; Zhiyou Fang; Xueran Chen

doi:10.1038/s41389-021-00361-8

Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation

Oncogenesis. 2021 Oct 27;10(10):72. doi: 10.1038/s41389-021-00361-8.

Authors

Xiaoqing Fan^#^{1

2

3}, Junqi Fan^#^{1

2}, Haoran Yang^{1

3

4}, Chenggang Zhao^{1

2}, Wanxiang Niu^{1

2}, Zhiyou Fang^{5

6}, Xueran Chen^{7

8}

Affiliations

¹ Anhui Province Key Laboratory of Medical Physics and Technology, 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, No. 96, Jin Zhai Road, Hefei, Anhui, 230027, China.
² University of Science and Technology of China, No. 96, Jin Zhai Road, Hefei, Anhui, 230031, China.
³ Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), No. 17, Lu Jiang Road, Hefei, Anhui, 230001, China.
⁴ Department of Laboratory Medicine, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui, 230031, China.
⁵ Anhui Province Key Laboratory of Medical Physics and Technology, 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, No. 96, Jin Zhai Road, Hefei, Anhui, 230027, China. zyfang@cmpt.ac.cn.
⁶ Department of Laboratory Medicine, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui, 230031, China. zyfang@cmpt.ac.cn.
⁷ Anhui Province Key Laboratory of Medical Physics and Technology, 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, No. 96, Jin Zhai Road, Hefei, Anhui, 230027, China. xueranchen@cmpt.ac.cn.
⁸ Department of Laboratory Medicine, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui, 230031, China. xueranchen@cmpt.ac.cn.

^# Contributed equally.

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.

Abstract

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