Arylsulfatase D promotes malignant phenotypes in glioblastoma cells and is linked to altered Hippo pathway phosphorylation.

Overview

1. Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, Hunan, China

Abstract

Introduction: Glioblastoma (GBM) is a highly aggressive malignant brain tumor with persistently poor clinical outcomes and few effective treatment options. Arylsulfatase D (ARSD), a lysosomal sulfatase implicated in several cancers, has not been fully characterized in GBM.

Methods: ARSD expression in GBM was evaluated using bioinformatic analyses and immunohistochemical validation. ARSD was overexpressed or knocked down in U87MG, U251MG, and A172 cells, and proliferation, three-dimensional spheroid growth, apoptosis, invasion, and Matrigel-based tube-like network formation were assessed. Merlin/LATS/YAP phosphorylation-related protein patterns were analyzed. Irosustat was further evaluated in a subcutaneous U87MG xenograft model.

Results: ARSD was upregulated in GBM tissues, and higher ARSD expression was associated with unfavorable patient survival. ARSD overexpression enhanced proliferation, three-dimensional spheroid growth, invasion, and Matrigel-based tube-like network formation while reducing apoptosis, whereas ARSD knockdown suppressed these malignant phenotypes. ARSD expression was associated with altered Merlin/LATS/YAP phosphorylation-related protein patterns, particularly changes in YAP1 abundance and phosphorylation status. In the xenograft model, Irosustat treatment altered YAP phosphorylation-associated protein patterns, enhanced tumor cell apoptosis, reduced tumor burden, and prolonged mouse survival.

Discussion: These findings indicate that ARSD facilitates GBM malignant behavior and is linked to Merlin/LATS/YAP phosphorylation-related signaling. Irosustat showed preliminary antitumor activity in the xenograft model; however, because Irosustat is not an ARSD-specific inhibitor, the in vivo findings should not be interpreted as evidence of selective ARSD inhibition.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE103224, at NCBI GEO; found in the text, “Bioinformatics analysis”

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 7 authors, 7 keywords, 39 references.

Cite

This paper

Li, X., Hou, Q., Tang, Y., Wang, N., Zhong, C., Xu, L., & Wang, J. (2026). Arylsulfatase D promotes malignant phenotypes in glioblastoma cells and is linked to altered Hippo pathway phosphorylation. Frontiers in oncology, 16, 1927290. https://doi.org/10.3389/fonc.2026.1927290

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