Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation
Xiaoqing Fan,
Junqi Fan,
Haoran Yang,
Chenggang Zhao,
Wanxiang Niu,
Zhiyou Fang,
Xueran Chen
Affiliations
Xiaoqing Fan
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Junqi Fan
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Haoran Yang
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Chenggang Zhao
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Wanxiang Niu
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Zhiyou Fang
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Xueran Chen
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
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.
