Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation

• Published in: Oncogenesis (New York, NY) Vol. 10; no. 10; p. 72
• Main Authors: Fan, Xiaoqing, Fan, Junqi, Yang, Haoran, Zhao, Chenggang, Niu, Wanxiang, Fang, Zhiyou, Chen, Xueran
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27-10-2021; Nature Publishing Group
• Subjects: 13/1; 13/100; 13/2; 13/44; 13/51; 13/89; 14/34; 38/77; 631/532/71; 631/67/1059/602; 631/67/1922; 64/60; Apoptosis; Brain cancer; Brain tumors; Cell Biology; Glioblastoma; Glioma; Growth factors; Human Genetics; Hypoxia-inducible factor 1; Hypoxia-inducible factors; Internal Medicine; Isocitrate dehydrogenase; Medicine; Medicine & Public Health; Mesenchyme; Oncology; Palmitoylation; Palmitoyltransferase; Precision medicine; Signal transduction; Smad3 protein; Stem cells; Transforming growth factor-b; Tumors
• ISSN: 2157-9024; 2157-9024
• DOI: 10.1038/s41389-021-00361-8

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.