HDAC7 drives glioblastoma to a mesenchymal-like state via LGALS3-mediated crosstalk between cancer cells and macrophages.

Autor:	Zhao S; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China.; Department of Neurosurgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China., Zhao R; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Wang C; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Ma C; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Gao Z; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Li B; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Qi Y; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Qiu W; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Pan Z; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Wang S; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Guo Q; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Qiu J; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Fan Y; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China., Guo X; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China.; Department of Neurology, Loma Linda University Health, Loma Linda 92350, California, USA., Xue H; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Deng L; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China., Li G; Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, China.; Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan 250012, China.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2024 Oct 21; Vol. 14 (18), pp. 7072-7087. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024).
DOI:	10.7150/thno.100939
Abstrakt:	Background: Glioblastoma multiforme (GBM) is an aggressive brain tumour for which current traditional treatment approaches have been unsuccessful, owing to the high genetic heterogeneity and immunosuppressive tumour microenvironment. Methods: Single-cell and spatial transcriptomic data revealed the niche-specific enrichment of mesenchymal-like (MES-like) GBM cells and monocyte-derived macrophages (MDMs); Gain- and loss-of-function assays of HDAC7 was confirmed both in vitro and in vivo assays. Mechanistically, mass spectrum, RNA immunoprecipitation (RIP), and co-immunoprecipitation assays were conducted. Results: We found that HDAC7, which upregulated by TRIM28-mediated sumoylation at the protein levels, inhibited SOX8 expression by mediating H3K27 deacetylation. And the down-regulated SOX8 facilitated the transcriptional activity of JUN, to induce LGALS3 secretion, which then bind to the membrane protein ITGB1 on GSC and MDMs in the autocrine and paracrine manners to facilitate the transformation of the mesenchymal phenotype of GBM and the M2 polarization of MDMs, respectively. In turn, LGALS3 could also secreted by M2 MDMs to promote MES transition of GBM in a paracrine manner, creating a positive feedback loop. In translational medicine, we found that blocking LGALS3 improved the therapeutic sensitivity of HDAC inhibitors. Conclusions: Our findings revealed the role of the novel HDAC7-H3K27ac-SOX8/JUN-LGALS3-ITGB1 axis in maintaining the crosstalk between MES GBM and M2 MDM, highlighting that HDAC7 and LGALS3 may serve as potential prognostic biomarkers and therapeutic targets in GBM. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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