GALNT2 sustains glioma stem cells by promoting CD44 expression

Liu, Yingying; Chen, Peisheng; Xu, Liufei; Wang, Bo; Zhang, Shengping; Wang, Xiangpeng

doi:10.18632/aging.204609

Cited by 4 publications

(1 citation statement)

References 35 publications

(39 reference statements)

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“…Elevated GALNT2 levels are linked to unfavorable outcomes in patients with glioblastoma multiforme (GBM). In a functional context, inhibiting GALNT2 disrupts the growth, self-renewal, and aggressive behavior of glioma stem-like cells, primarily by downregulating CD44 expression ( 64 ). GALNT2 has been shown to contribute to the enhanced aggressiveness of colorectal cancer cells, doing so in part by modulating the AXL pathway ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

Zhang,

Lin

et al. 2024

Front. Immunol.

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BackgroundThe tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD.MethodUtilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2.ResultsOur study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD’s microenvironment. We underscored pDCs’ role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2’s function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment.ConclusionThe creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

Zhang,

Lin

et al. 2024

Front. Immunol.

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Insights into the role of glycosyltransferase in the targeted treatment of gastric cancer

Wang,

Zhang,

Luo

et al. 2024

Biomedicine & Pharmacotherapy

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NRP1 Induces Enhanced Stemness and Chemoresistance in Glioma Cells <i>via</i> YAP

Jin,

Wang

et al. 2024

Biological & Pharmaceutical Bulletin

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Neuropilin-1 (NRP1), a transmembrane glycoprotein, plays an important role in the malignant progression of gliomas; however, its role in chemoresistance is not fully understood. In this study, we observed the effects of NRP1 on the stemness and chemoresistance of glioma cells and the mediating role of Yes-associated protein (YAP). We constructed NRP1 overexpressing LN-229 glioma cells. Cells were treated with recombinant NRP1 protein (rNRP1) and the YAP inhibitor Super-TDU when necessary. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the sensitivity of cells to temozolomide (TMZ). Sphere and clone formation assays were performed to detect the sphere-and clone-forming abilities of cells. Western blotting was performed to detect cellular CD133, CD44, p-LATS1, and p-YAP protein expression. Immunofluorescence and flow cytometry were used to detect the subcellular localization of YAP and apoptosis, respectively. We found that both NRP1 overexpression and rNRP1 treatment enhanced self-renewal, TMZ resistance, and CD133 and CD44 protein expression in LN-229 cells. NRP1 overexpression and rNRP1 treatment also induced LATS1 and YAP dephosphorylation and YAP nuclear translocation. Super-TDU inhibits NRP1 overexpression-induced enhanced self-renewal and TMZ resistance in LN-229 cells. Our study suggests that NRP1 induces increased stemness in glioma cells, resulting in chemoresistance, and that this effect is associated with YAP activation.

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GALNT2 sustains glioma stem cells by promoting CD44 expression

Cited by 4 publications

References 35 publications

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells

Insights into the role of glycosyltransferase in the targeted treatment of gastric cancer

NRP1 Induces Enhanced Stemness and Chemoresistance in Glioma Cells <i>via</i> YAP

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