Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

Xu, Anqi; Wang, Xizhao; Luo, Jie; Zhou, Mingfeng; Yi, Renhui; Huang, Tengyue; Lin, Jie; Wu, Zhi‐Yong; Xie, Congying; Ding, Shilei; Zeng, Yu; Song, Ye

doi:10.1038/s41419-021-03424-1

Cited by 17 publications

(8 citation statements)

References 58 publications

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“…Therefore, validation of the mechanism of the MEOX2 isoform in glioma warrants further investigation. PI3K/AKT, Wnt/β-catenin, Hippo pathways are closely related with EMT and focal adhesion in glioma, thus the mechanism of MEOX2 in glioma might be more complicated than this study presents [ 24 , 42 , 43 ]. Thus, we will further explore the roles and molecular mechanisms of MEOX2 in glioma, and provide insight into novel therapeutic strategies for glioma.…”

Section: Discussionmentioning

confidence: 99%

MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma

Chen

Wang

et al. 2022

Cell Death Dis

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Nuclear transcription factor Mesenchyme Homeobox 2 (MEOX2) is a homeobox gene that is originally discovered to suppress the growth of vascular smooth muscle and endothelial cells. However, whether or not it is connected to cancer is yet unknown. Here, we report that MEOX2 functions as a tumor-initiating element in glioma. Bioinformatic analyses of public databases and investigation of MEOX2 expression in patients with glioma demonstrated that MEOX2 was abundant at both mRNA and protein levels in glioma. MEOX2 expression was shown to be inversely linked with the prognosis of glioma patients. MEOX2 inhibition changed the morphology of glioma cells, inhibited cell proliferation and motility, whereas had no effect on cell apoptosis. Besides, silencing MEOX2 also hampered the epithelial-mesenchymal transition (EMT), focal adhesion formation, and F-actin assembly. Overexpression of MEOX2 exhibited opposite effects. Importantly, RNA-sequencing, ChIP-qPCR assay, and luciferase reporter assay revealed Cathepsin S (CTSS) as a novel transcriptional target of MEOX2 in glioma cells. Consistently, MEOX2 causes glioma tumor development in mice and greatly lowers the survival period of tumor-bearing mice. Our findings indicate that MEOX2 promotes tumorigenesis and progression of glioma partially through the regulation of CTSS. Targeting MEOX2-CTSS axis might be a promising alternative for the treatment of glioma.

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Section: Discussionmentioning

confidence: 99%

MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma

Chen

Wang

et al. 2022

Cell Death Dis

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“…Aneuploidy is one of the most common phenomena seen in most tumors (Rajagopalan and Lengauer, 2004), and Cut overexpression is also (Sansregret and Nepveu, 2008) reported in a diverse classes of cancer. There are several tumors, including glioma, where CUX1 overexpression has been reported and considered among driver mutation (Feng et al, 2021; Griesmann et al, 2021; Sansregret and Nepveu, 2008; Xu et al, 2021). A in vitro study shows that mammalian CUX1 has the potential to cause chromosomal instability (Sansregret et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cut homeodomain transcription factor is a novel regulator of cortex glia morphogenesis and maintenance of neural niche

Yadav¹,

Das²,

Mishra³

et al. 2022

Preprint

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Cortical glia in Drosophila central nervous system forms a niche around neural stem cells (NSCs) and their progeny for necessary signals to establish cross-talk with their surroundings. These cells grow and expand their thin cytoplasmic extensions around neural cell bodies in the nervous system. Although essential for the development and function of the nervous system, how these cells make extensive and intricate membrane networks remain largely unknown. Here we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortical glial cells impacting NSC homeostasis. Focusing on the thoracic ventral nerve cord (tVNC), we found that Cut is required for normal growth and development of cortical glial cells. We also highlight that levels of Cut expression play an essential role in the cytoplasmic membrane network growth around the neural cells. Loss of Cut in cortical glia results in a substantial reduction in their cytoplasmic extensions and network around cell bodies of NSCs and their progeny, whereas its overexpression induces the overall growth of cortical glia main branches at the expense of side ones. We also note a striking gain in the nuclear size and volume of cortical glial cells upon Cut overexpression. Furthermore, constitutively high Cut levels increase DNA content in these cells more than threefold, indicating an interference with the splitting of nuclei during endomitosis. Since cortical glia makes syncytial membrane networks around neural cells, the finding identifies Cut as a regulator of glial growth and endomitosis to support a functional nervous system. It is the first report that highlights a novel function of Cut in regulating the growth and branching of cortical glial cells and control over endomitosis.

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“…17,18 Although the central nervous system (CNS) lacks this critical tissue component, 19 a range of changes in EMT-associated activators, including decreased expression of various epithelial markers (occludins, E-cadherin, ZO-1) and increased expression of mesenchymal markers (N-cadherin, vimentin, and fibronectin), were observed during glioma progression. 20 Given these observations, the terms "proneural-to-mesenchymal transition" or the "EMT-like" process have been proposed. 21,22 A better understanding of the molecular regulation of the EMT-like process during tumor spreading will help to provide potential therapeutic interventions to target this program when treating glioma.…”

Section: Introductionmentioning

confidence: 99%

Interferon‐γ inducible protein 30 promotes the epithelial–mesenchymal transition‐like phenotype and chemoresistance by activating EGFR/AKT/GSK3β/β‐catenin pathway in glioma

Chen

et al. 2023

CNS Neurosci Ther

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AimsPrevious studies have indicated that IFI30 plays a protective role in human cancers. However, its potential roles in regulating glioma development are not fully understood.MethodsPublic datasets, immunohistochemistry, and western blotting (WB) were used to evaluate the expression of IFI30 in glioma. The potential functions and mechanisms of IFI30 were examined by public dataset analysis; quantitative real‐time PCR; WB; limiting dilution analysis; xenograft tumor assays; CCK‐8, colony formation, wound healing, and transwell assays; and immunofluorescence microscopy and flow cytometry.ResultsIFI30 was significantly upregulated in glioma tissues and cell lines compared with corresponding controls, and the expression level of IFI30 was positively associated with tumor grade. Functionally, both in vivo and in vitro evidence showed that IFI30 regulated the migration and invasion of glioma cells. Mechanistically, we found that IFI30 dramatically promoted the epithelial–mesenchymal transition (EMT)‐like process by activating the EGFR/AKT/GSK3β/β‐catenin pathway. In addition, IFI30 regulated the chemoresistance of glioma cells to temozolomide directly via the expression of the transcription factor Slug, a key regulator of the EMT‐like process.ConclusionThe present study suggests that IFI30 is a regulator of the EMT‐like phenotype and acts not only as a prognostic marker but also as a potential therapeutic target for temozolomide‐resistant glioma.

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Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

Cited by 17 publications

References 58 publications

MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma

MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma

Cut homeodomain transcription factor is a novel regulator of cortex glia morphogenesis and maintenance of neural niche

Interferon‐γ inducible protein 30 promotes the epithelial–mesenchymal transition‐like phenotype and chemoresistance by activating EGFR/AKT/GSK3β/β‐catenin pathway in glioma

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