Unveiling the impact of SUMOylation at K298 site of heat shock factor 1 on glioblastoma malignant progression

Xiang Li; Zongqi Wang; Bixi Gao; Kun Dai; Jiang Wu; Kecheng Shen; Guangzhao Li; Xiaowang Niu; Xin Wu; Longyuan Li; Haitao Shen; Haiying Li; Zhengquan Yu; Zhong Wang; Gang Chen

Neoplasia: An International Journal for Oncology Research (Nov 2024)

Unveiling the impact of SUMOylation at K298 site of heat shock factor 1 on glioblastoma malignant progression

Xiang Li,
Zongqi Wang,
Bixi Gao,
Kun Dai,
Jiang Wu,
Kecheng Shen,
Guangzhao Li,
Xiaowang Niu,
Xin Wu,
Longyuan Li,
Haitao Shen,
Haiying Li,
Zhengquan Yu,
Zhong Wang,
Gang Chen

Affiliations

Xiang Li: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China; Department of Neurosurgery, Xinghua People's Hospital Affiliated to Yangzhou University, Xinghua 225700, China
Zongqi Wang: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Bixi Gao: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Kun Dai: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Jiang Wu: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Kecheng Shen: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Guangzhao Li: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Xiaowang Niu: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Xin Wu: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Longyuan Li: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Haitao Shen: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Haiying Li: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Zhengquan Yu: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China
Zhong Wang: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China; Corresponding authors at: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
Gang Chen: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China; Corresponding authors at: Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China

Journal volume & issue: Vol. 57
p. 101055

Abstract

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Background: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. Methods: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. Results: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. Conclusion: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

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